turning point - dana–farber cancer institute

Turning PointFrom the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute

Holding PromiseTargeted Therapies for Women’s Cancers

2012

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SuSan F. Smith Center For

Women’S CanCerS

LeaderShip

J. Dirk Iglehart, MD Director, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute Chief, Section on Cancer Biology, Brigham and Women’s Hospital

Eric Winer, MDDirector, Breast Oncology Center, Dana-Farber Cancer Institute

Ross Berkowitz, MD Director, Gynecology and Gynecologic Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute

Ursula Matulonis, MDMedical Director, Gynecologic Oncology, Dana-Farber Cancer Institute

Jay Harris, MDChair, Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital

Judy Garber, MD, MPHDirector, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute

Myles Brown, MDChief, Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute

Candace S. Lowe, ScDAdministrative Director, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute

ViS it ing Committee

Susan F. Smith* (Chair)

Jane P. Jamieson* (Co-chair)

Barbara P. Allen

Norman J. Cantin

Carie Capossela

Patrick Carney

Sarit S. Catz

Patricia Hennessey Chadwick

Monica Chandra

Anne E. Columbia

Julia D. Cox

Randi Gilbert Cutler

Charles A. Dana III*

John A. Duffy, Sr.

Mary Schneider Enriquez

Eileen E. Epstein

Nina Sing Fialkow

Deborah S. First*

Tracey E. Flaherty

Marian L. Heard*

Matina S. Horner, PhD

William S. Karol*

Melissa Chamberlain Leet

Stacey J. Lucchino

Melanie D. Mace

Anne Punzak Marcus

Alan B. Miller

Susan P. Miller

Ruth A. Moorman

Elizabeth M. Pohl*

Amy Zarkin Reiner*

Margaret M. Reynolds

Judith P. Schlager*

Kristine S. Shadek

Laurene M. Sperling

Jill M. Stansky

Jean C. Tempel*

Beth F. Terrana*

Karen L. Webster*

Gwill E. York

*Trustee, Dana-Farber Cancer Institute

Turning Point2012

1 Susan F. Smith Center for Women’s Cancers

4 Ask the Care TeamAge for screening tests; inherited vs. genetic cancers

6 Research RoundupNew drug for ovarian cancer subtype; advocates begin study; how cells specialize; breast cancer and Li Fraumeni syndrome; standardizing care; male hormone in breast tumors; strengthening genetic research

10 Holding Promise A look at the evolution of breast cancer treatment and how targeted techniques are more effective

14 Silencing the SignalsFinding genetic mutations that drive endometrial and cervical cancers

17 Bridges and PartnershipsLinking research and care atDana-Farber

20 Survivor SpotlightMargaret Winchester is passionate advocate; Pam Zwemer is always prepared

Turning Point is published for supporters of the Susan F. Smith Center for Women’s Cancers (SSC). To learn more about the SSC, call Administrative Director Candace S. Lowe, ScD, at 617-632-2675.

Comments, suggestions, and requests to be added to or deleted from the mailing list may be sent to:

Turning Point Dana-Farber Cancer InstituteDepartment of Communications 450 Brookline Avenue, OS300 Boston, MA 02215or call 617-632-4090 or email [email protected]

Editor: Christine Cleary

Art Director: John DiGianni

Managing Editor: Eric Schuller

Design: Lee Whale

Contributors: Scott Edwards, Robert Levy, Debra Bradley Ruder

Production: Jacqueline Czel

Photography: Sam Ogden, Don Watson (page 6)

10

14

17

Membership listing current as of April 1, 2012.

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1Susan F. Smith Center for Women’s Cancers

J. Dirk Iglehart, MD

Susan F. Smith Center for Women’s Cancers

Almost 300,000 women in the United States will learn this year that they have breast

or gynecologic cancer, and the Susan F. Smith Center (SSC) for Women’s Cancers

at Dana-Farber is poised to help – either directly through patient care, or indirectly

through research and teaching.

Under the leadership of J. Dirk Iglehart, MD, the SSC exemplifies Dana-Farber’s 50-50 balance, unique among cancer centers: an equal dedication to scientific discovery and patient care. Scientists are inspired by the belief that their efforts might save, or improve, the life of a patient just a few steps away from the lab. Similarly, clinicians can easily consult with basic scientists to better under-stand the molecular mechanisms behind a certain type of cancer or treatment. The bench to bedside paradigm goes one step further – back to bench – when refinements are needed.

Looking BackThe research collaborative that would one day

become the Susan F. Smith Center for Women’s Cancers began at Dana-Farber in 1993. At the time, scientists were discovering that cancers of the breast and female reproductive tract were more closely related at a basic biological level than had been thought. It was also becoming clear that women’s cancers – wherever they originate – unite patients in a sisterhood of shared concern and experience.

The idea for the center arose in a meeting between David Livingston, MD, and Dana-Farber trustee Susan F. Smith, in which Dr. Livingston suggested combining the Institute’s then-separate breast and gynecologic cancer programs. This notion of a center dedicated to studying and treating all women’s cancers captured Mrs. Smith’s imagination. Her determination, and that of many others, to make it a reality has been a steady force behind the center’s growth.

Since the research collaborative began, the center

expanded its scientific portfolio many times, pro-ducing scientific advances that shaped the course of patient care. Then, in 1996, the clinical service opened, providing unparalleled patient care. In cancer treatment, outstanding clinical care goes hand in hand with research, which often brings the laboratory efforts of the program closer to patients.

A few years later, Dana-Farber’s Board of Trustees established a Visiting Committee that informs scientists and physicians about the public’s major interests and questions about cancer care for women, spreads the word about recent advances at Dana-Farber, and helps raise funds for research. Its leader since its founding has been Mrs. Smith, joined by trustee Jane Jamieson as co-chair in 2009.

The Visiting Committee has sparked a range of innovations. One of the most far-reaching was the development of the Executive Council, which has mobilized thousands of women in Greater Boston to learn about, and support, research at Dana-Farber into women’s health and women’s cancers.

Throughout the years of providing care to women with cancer, a common theme has begun to emerge: care needs to be individualized. See the article beginning on page 10 for an exploration of how physicians use surgery and radiation more con-servatively to achieve success.

A Hint of the FutureThe grouping of scientists nearly 20 years ago

– specialists in breast cancer joined with experts in gynecologic cancers – foreshadowed a host of later discoveries about the basic biology of tumors. It turned out that cancers once thought to be radically

Eric Winer, MD

Ursula Matulonis, MD

Judy Garber, MD

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Turning Point 2012 www.dana-farber.org


different because they arose in different tissues and organs can harbor surprising similarities.

“It has become increasingly apparent that many of these diseases share a great many molec-ular features,” says Dr. Iglehart. “One example is PI3 kinase, a protein involved in a pathway that is frequently altered in both breast and gyne-cologic cancers.”

Today, as cancers are identified by their genetic signatures as well as by their tissue of origin, more precise therapies will become possible. See “Ask the Care Team,” on page 5, to understand Dana-Farber’s groundbreaking research in inherited genes such as BRCA1 and BRCA2 that cause certain cancers, and the genetic mutations that lurk behind all cancers.

The SSC’s clinical areas now occupy two floors of Dana-Farber’s Yawkey Center for Cancer Care. Patients with breast cancer are treated on the ninth floor, and women with gynecological cancers on

the 10th. SSC physicians and scientists don’t have to travel far to meet: an enclosed bridge connects clinical units with corresponding units in the Richard A. and Susan F. Smith Research laboratories. This proximity spurs translational research that converts scientific advances into new treatments. The article beginning on page 17 introduces several pairs of basic and clinical researchers whose work speeds discoveries from bench to bedside.

Working TogetherAn increase in patient visits since the early days

of the SSC is mirrored in the expansion of our clinical staff.

When Eric Winer, MD, director of the Breast Oncology Center, arrived at Dana-Farber in 1997, five medical oncologists specialized in breast cancer. Now, there are more than 20. When Ursula Matulonis, MD, became director of Gynecologic Oncology in 2004, she was the program’s only

2011 Milestones2011 Milestones

• Anthony Letai, MD, PhD, is applying a technique he developed for blood cancers, called BH3 profiling, to deter-mine the degree to which ovarian cancer cells are likely to respond to chemo-therapy. His findings have led Ursula Matulonis, MD, and Joyce Liu, MD, to design a new trial to evaluate a bcl-2 inhibitor in patients with ovarian cancer.

• To further understand which genetic mutations drive cervical cancer, Alexi Wright, MD, is overseeing the screening of 100 previously collected samples, using gene-scanning tech-

nology to find shared mutations. See page 16 to learn more about Dr. Wright’s work.

• Thomas Roberts, PhD, and Jean Zhao, PhD, continued their work involving the role of PI3-kinase in breast cancer. Relying on genetically engineered mice, Dr. Zhao has identi-fied pathways of resistance to PI3-kinase inhibitors. In separate studies, Dr. Roberts found that tumor cells do not respond to the inhibitor if the MYC protein is overactive, mirroring Dr. Zhao’s discovery that this appears to

bypass the PI3-kinase block.

• Based on research by Drs. Robertsand Zhao, Eric Winer, MD, and Ian Krop, MD, PhD, are leading studies for women with HER2- positive breast cancer to determine which PI-3-kinase inhibitors and/or which combinations of drugs would be most effective. As part of the same project, Andrea Myers, MD, PhD, is leading a clinical trial evaluating an inhibitor in patients with endometrial cancer whose tumors have PI-3 kinase inhibitors. See article beginning on page 17.

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oncologist focusing solely on ovarian cancer. Now, there are two additional physician/scientists who specialize in ovarian cancer treatment and research.

Over the past decade, the number of breast cancer surgeons has risen from three to 10, the number of breast cancer patholo-gists from two to five, and the number of gynecologic patholo-gists from one to four.

As the clinical and scientific team has grown, so have the opportunities for collaboration. “The extent of cross-disciplinary research we’re able to do has risen dramatically,” Dr. Iglehart remarks. “For example, our Tissue Resource for Research, for

both breast and gynecologic tumor samples, has streamlined our process and spurred creative interchange among our scientists.” See “Two Programs Collect Tissue for Research,” on page 9.

A determination to create ways for people to work together has always been the center’s hallmark, Mrs. Smith says. “I look back with pride at what we’ve accomplished, not only in the research area, but in the compassion with which we’ve treated patients. I look forward to and hope for more and deeper col-laboration between the research and clinical faculty to translate scientific findings into better and more effective treatments for patients.”

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Ask the Care Team

At what age should I begin getting breast and cervical cancer screenings, and at what age will I no longer need them?

Thanks in part to screening programs, death rates from breast and cervical cancer have dropped dramatically in recent years. “For certain types of cancer, screenings can detect a malignancy in its earliest stages, when it is more easily and successfully treated,” says Judy Garber, MD, MPH, the director of Dana-Farber’s Center for Cancer Genetics and Prevention. Deciding when to begin – and end – these screenings, however, is not so straightforward.

While mammography is not perfect, it is the best screening tool currently available, says Eric Winer, MD, the director of the Breast Oncology Center at Dana-Farber. There is, however, considerable controversy regarding the age at which you should begin getting mammograms.

In 2009, the U.S. Preventive Services Task Force (USPSTF) recommended that, beginning at age 50, women should have a mam-mogram every two years, and that more evidence is needed to make a recom-mendation for or against screening after age 74. The American Cancer Society (ACS), however, advises women to begin routine annual screening at age 40 and continue for as long as they remain in good health.

Dana-Farber experts say that only women at highest risk for breast cancer should begin mammography before age 40. After age 40, however, you can have an annual mammogram, based

on your preferences and your doctor’s recommendations. All women should begin yearly screening at age 50.

The American Congress of Obste-tricians and Gynecologists, ACS, and USPSTF recently updated their guide-lines for cervical cancer screening, as well. They agree on several main points. In general, screening with Pap tests should start at age 21 in other-wise healthy women and continue every year or two until age 30. Then, women with at least three normal Pap tests may undergo Pap testing every three years, with or without co-testing for high-risk HPV, the virus that causes some cervical cancers.

If you have had normal lifetime screening, you may discontinue Pap tests between ages 65 and 70, but should still have routine gynecologic care. If you have never been screened, or have a history of high-grade dys-plasia (a condition in which cells abnormally grow on the surface of the cervix), you are at highest risk of developing cervical cancer and should receive ongoing screening regardless of your age.

Dana-Farber breast and cervical cancer specialists encourage you to speak with your physician about appropriate screening based on your age, medical history, and risk factors.

4 Turning Point 01 www.dana-farber.org

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What is the difference between research involving genes in people and research involving genes in tumors?


Human cells have about 22,000 genes, which consist of DNA packed into chromosomes inside the cell nucleus. Genes control a wide range of functions, including cell growth and division. If DNA is damaged during a cell’s life, certain genes work to repair the damage. Over time, however, those repair genes themselves may become ineffective, allowing DNA damage to accumulate.

If a cell acquires enough errors or mutations in certain genes, it may become cancerous – able to grow and divide without control. Such mutated genes exist only within the cancer itself, not the rest of the body. For that reason, they make excellent targets for so-called “smart” drugs that take aim at specific muta-tions. The advantage of such drugs is that they can attack cancer cells while producing less harm to normal cells than traditional chemotherapy. Genetic defects that appear only in cancer cells are known as “somatic” mutations.

Other mutations in cancer are known as “germline.” These are inherited from a parent or arise early in fetal development and are found in every cell of affected individuals. “You inherit two copies of most genes in your body – one from your mother and one from your father,” explains Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber. “If you have a germline mutation in one copy of a particular gene, the other copy would be normal.”

It generally requires mutations in both copies for cancer to occur. People born with a mutation in one copy are likely to acquire a mutation in the other more quickly than those who begin life without these mutations – much as a baseball batter with one strike will probably reach a two-strike count faster than a batter with no strikes.

Scientists have discovered a variety of such cancer-sus-ceptibility genes – such as BRCA1 and BRCA2. In addition, specialists can screen people with a family history of cancer to determine if they carry mutations in these genes.

Cancer research is concerned with both varieties of mutation. Some scientists are looking for somatic mutations associated with cancer so they can develop new targeted therapies, while others are tracking potential germline muta-tions in families where cancer has run like a thread through the generations.

The Profile research project in cancer genomics launched last year by Dana-Farber and Brigham and Women’s Hospital (see page 9) is concerned with both types of mutations. In one part of the project, adult patients can have their leftover tumor tissue screened for nearly 500 somatic mutations involved in cancer. In another part, they can donate normal cells – from a simple cheek swab or blood draw – for germline studies of genes that may predispose people to developing certain cancers.

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Advocates Measure Value of Reporting Results

Anti-angiogenesis Drugs May Work in Ovarian Cancer Subtype

A group of advocates who provide a patient perspective to clinical investigators in the Susan F. Smith Center for Women’s Cancers (SSC) have now become researchers in their own right.

The Breast Cancer Advocacy Group (BCAG), composed chiefly of breast cancer patients and survivors, has begun a pilot study to measure the value of reporting clinical trial results to participants.

“Patients are, understandably, focused on their own out-comes when they join clinical trials, but, in most cases, they never find out the overall result of the study,” says Elizabeth Frank, lead patient advocate for the BCAG. Ann Partridge, MD,

director of Dana-Farber’s Adult

Survivorship Program, and Eric Winer, MD, director

of the SSC’s Breast Oncology Center, are co-investigators.The study will develop a protocol for returning results to

participants, evaluate the process and materials, and survey two sets of patients: those who receive results and those who do not. Key among the study’s goals is one very simple inter-vention: a thank-you to participants.

Although BCAG members are called “patient advocates,” Frank explains that their roles are different from traditional advocates, who tend to support patient rights. “We work solely on the research side, reviewing concepts and protocols for clinical trials from a patient’s perspective,” says Frank, who has a background in market research and program evaluation. “It can be very hard work.” For example, the advocates might recommend revisions to research questions so they more closely reflect the concerns of patients.

Other duties include helping investigators develop grant pro-posals for a Breast SPORE (Specialized Program of Research Excel-lence) from the National Cancer Institute, reviewing applications for SPORE-funded Career Development Awards, and working hand-in-hand with investigators to design research studies.

“Liz and the other advocates have played an instrumental role in research design that I think is stimulating and produc-tive,” says Nancy Lin, MD, clinical director of the Breast Oncology Center in the SSC.

In emphasizing the importance of examining the way par-ticipants receive clinical trial results, Dr. Lin adds that the new study will help researchers understand the impact of delivering such results and identify the best approach for doing so. “In addition, the study will help us develop standard guidelines

that investigators can turn to in the future.”

Dana-Farber scientists have identi-fied a subtype of ovarian cancer able to grow its own blood vessels, suggesting that such tumors might be especially susceptible to “anti-angiogenic” drugs that block blood vessel formation.

In a study published earlier this year, investigators estimate the subtype may account for a third of all serous ovarian cancers, a common cancer of the surface of the ovaries. The discovery may spur clinical trials to see if patients

with the subtype can benefit from anti-angiogenic therapies now being tested in other cancers.

“We’ve shown that serous ovarian cancer exists in at least one distinct subtype at the molecular level, raising the possibility that it will be vulnerable to therapies directed at its molecular weaknesses,” says John Quackenbush, PhD, who, along with his Dana-Farber colleague Ursula Matulonis, MD, served as the study’s co-senior author.

Researchers scanned the activity of thousands of genes in high-grade serous ovarian cancers, taken from 129 patients with an advanced stage of the disease, then sifted the data with a specially designed algorithm. They identified a subtype in which genes involved in blood vessel growth were highly expressed, and confirmed their findings by drawing on other published studies involving more than 1,500 patients.

Research advocates in the Susan F. Smith Center review protocols for studies involving women’s cancers.


Research Roundup

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Scientists Identify Breast Cancer Features in Rare DisorderBreast cancer in women with Li Fraumeni Syndrome

(LFS) – a rare, inherited cancer-susceptibility disorder – is likely to have certain characteristics that can be used to guide treatment, new research by Dana-Farber scientists and an international consortium of associates has found.

The investigators learned that breast tumor cells in women with the syndrome tend to have two specific attributes – hormone receptors and an overabundance of receptors known as HER2 – suggesting that treatments targeted at those recep-tors can be especially effective in these patients.

People with LFS inherit a mutation in a tumor-suppressor gene known as TP53, placing them at increased risk for cancers of the breast, bone, brain, blood, and other tissues,

predominantly in childhood and early adulthood. The risk of breast cancer in women with LFS is approximately 49 percent by age 60, with a significant risk before age 40.

“Recent studies have suggested that breast cancers in women with LFS are positive for hormone receptors and HER2, but the number of tumors analyzed in those studies was relatively small,” says the new study’s senior author, Judy Garber, MD, MPH, director of the Center for Cancer Genetics and Prevention at Dana-Farber. “By working with an international group of colleagues, we were able to extend that analysis to additional samples. The results will help us more closely match treatment to the specifics of each patient’s disease.”

Parents often share household responsibilities, one handling a chore while the other relaxes. Something quite similar happens within the human genome: although we all inherit two copies of each gene – one from our mother and one from our father – both copies are not always active at the same time.

Such single-gene activation plays a key role during the development of many nerve cells, helping map their con-nections within the brain. The process is also at work in the immune system, where it leads to the creation of slight variations in certain disease-fighting cells, enabling the body to counter a wide range of infectious agents.

At Dana-Farber, Alexander Gimelbrant, PhD, is exploring why some genes consistently favor the expres-sion of DNA from one parent or the other. He and his colleagues have found that this kind of preferential treatment is hardly a rare event, but occurs in many hundreds of human genes.

Dr. Gimelbrant is currently building a map of gene activation, showing which genes are likely to have one copy on and one copy off in different types of cells in both humans and mice.

“We’re particularly interested in

how this uneven activation contrib-utes to the progression of cancer,” Dr. Gimelbrant says. “The more we under-stand the process, the better we’ll be able to intervene in a way that impairs the development of cancer.”

Having one gene copy turned on (pink) and the other copy turned off (blue) may contribute to cancer.


Exploring How Cells Specialize

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Research Roundup

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Setting Standards for Cancer CareThere’s still room for improvement in national efforts

to produce guidelines for high-quality cancer care. Look no further than a study in the February 2012 issue of the Journal of the American Medical Association, which showed that nearly half of women who had lumpectomies for breast cancer underwent second operations they may not have needed – all because surgeons don’t yet agree on guidelines for the most common operation for breast cancer. The study was based on the medical records of more than 2,000 women treated at four hospitals nationwide.

At Dana-Farber, Michael Hassett, MD, MPH, is working with colleagues to develop quality measures based on evi-dence-based practices, and optimize the delivery of cancer care. A breast oncologist in the Susan F. Smith Center for Women’s Cancers, Dr. Hassett conducts research and serves on a number of advisory panels.

“Whenever you’re measuring quality, you want to identify the best treatment options for a particular group of people and see how often these recommended treatments are given,” says Dr. Hassett. “For example, if evidence shows that breast cancer patients who have a lumpectomy have better outcomes if they get follow-up radiation therapy, our quality measure should be to see how many women are getting radiation. If we find that 20 percent of patients at a certain organization don’t get radiation therapy, that’s low quality care.”

Dr. Hassett works with colleagues at Dana-Farber and other experts to develop measures that can be used by hos-pitals, clinics, and health systems to help reduce the gap between ideal and actual care – that is, the difference between what evidence identifies as recommended care and what patients actually receive.

“The concept of meaningful use, which encourages health care organizations to use electronic health records in ways that help us measure successes and quality, is becoming part of health care reform,” Dr. Hassett says. “To get incen-tive payments from Medicare and Medicaid, doctors and hospitals will need to show that they are meeting certain quality guidelines.”

This same idea applies to other endeavors, Dr. Hassett says, such as ‘pay for performance,’ where private insurers provide incentives to health care providers who meet certain quality or performance targets. Organizations such as the Joint Commission and governmental agencies are exploring how quality measures can be used to ensure patients are getting the best possible care, without unduly raising costs.

Michael Hassett, MD, PhD, compares recommended care with what patients actually receive.

To get Medicare payments after

new rules go into effect in 2013,

health care organizations will need

to show that they are meeting certain

quality guidelines.

Research Roundup

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How Male Hormone Can Fuel Breast TumorsAndrogen, the hormone responsible for producing male

sexual characteristics, also fuels the growth of some breast tumors in women. Dana-Farber scientists recently became the first to trace a molecular circuit by which the hormone accomplishes this, revealing several points where the circuit could potentially be cut short – and tumor growth stopped – by new therapies.

“We identified a special subtype of breast cancer that grows in response to androgen instead of estrogen, and have mapped the signaling pathways involved in its growth,” says Dana-Farber’s Myles Brown, MD, who led the research. “We’ve also demonstrated that drugs capable of blocking these pathways can inhibit tumor growth.”

The research began when Dr. Brown and his colleagues investigated a distinctive group of breast tumor cells, found in 5 to 10 percent of patients with the disease. Unlike other varieties of breast tumor cells, these had many receptors for androgen, none for estrogen, and an overabundance

of a protein called HER2. When the cells were exposed to androgen, they proliferated.

Analysis of the tumor cells’ genetic material showed that the androgen receptor activates two “transmission lines” for growth signals. The pathways, named for important proteins within them (WNT and HER2), play central roles in cell division and proliferation.

When researchers used drug molecules to handcuff the androgen receptor or the WNT or HER2 proteins in these cells, tumor growth stopped, both in laboratory cell cultures and in mice grafted with the cells.

“Therapies that shut down proteins in the androgen receptor, WNT, and HER2 pathways have the potential to be effective anti-tumor agents for women with this variety of breast cancer,” Dr. Brown says. “We hope combination therapies that target proteins at different points in these pathways will have the greatest chance for success.”

Two Programs Collect Tissue for ResearchDana-Farber continues to advance

the fields of genetic analysis and cancer research with two programs launched last year. First, the Susan F. Smith Center for Women’s Cancers (SSC) created the Tissue Resource for Research (TRR), a state-of-the-art system to collect and store tissues used for research in breast and gynecologic cancers.

In a similar effort, Dana-Farber and Brigham and Women’s Hospital announced the launch of Profile, a large-scale research program for all types of cancer in adults. It will establish an exten-sive genomic database for studies that seek to improve the effectiveness, safety, and precision of future cancer treatments.

While both programs aim to strengthen cancer research, they each have a different focus. The TRR, which was made possible by a $5 million initia-tive from the SSC Executive Council, collects samples from consenting patients with breast or gynecologic cancers, and scientists use those samples to pursue a

diverse range of research into women’s cancers. Profile has a more defined goal: scanning samples from consenting Dana-Farber adult patients for a specific set of genetic mutations that are known or suspected of being linked to cancer.

“While Profile is an effort to build an unprecedented genomic database, it is a very targeted initiative,” says J. Dirk Iglehart, MD, director of the SSC. “The TRR is much more of a discovery tool, providing researchers with tissue that can be used in many different research efforts and tests – genetic and otherwise.”

Patients who donate their tissue to the TRR can also participate in Profile, Dr. Iglehart says. The TRR samples, which are typically gathered during a biopsy or surgery, are preserved and protected for researchers seeking to find better ways to diagnose, prevent, and treat cancer in the future.

“The TRR is an incredibly helpful research tool that not many other facilities have,” Dr. Iglehart says. “Many

people assume that tumor tissue auto-matically gets saved for research, but in fact, it is destroyed at most hospitals. There are significant costs associated with storing it, obtaining patients’ consent, and maintaining quality. Thanks to the Executive Council’s initia-tive, we can save this tissue and ensure that it will be used for discovery.”

Research Roundup

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by Robert Levy

Holding PromiseTargeted Approaches for Breast Cancer Treatment

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WWhen Eileen Epstein was diagnosed with a common type of non-invasive breast cancer in 2002, her treatment plan was straightforward. She underwent a lumpectomy, in which the cancerous tissue and a small margin of healthy tissue was sur-gically removed, followed by six weeks of radiation therapy.

The treatment was a success: aside from some fatigue caused by the radiation, she had no adverse side effects and was cancer-free until last year, when a checkup revealed a small, invasive tumor in the other breast. As before, she received a lumpectomy and a cycle of radiation therapy. She also began taking an aromatase inhibitor, a targeted drug designed to arrest any rogue cancer cells that may have remained in her system.

From the time of her first diagnosis through both courses of treatment at Dana-Farber, Epstein, who lives with her husband, Mark, in Portsmouth, R.I., made a point of not becoming anxious about her future. “When I know I’m in good hands, I don’t worry,” says Epstein, the mother of three grown children.

Epstein’s treatment is the product of countless advances in the medicines, surgical procedures, and radiation techniques used to treat breast cancer – all of them spurred by a better understanding of the basic biology of the disease, and an emphasis on precision. A generation earlier, the course of her treatment, and of her life afterward, would likely have been quite different.

J. Dirk Iglehart, MD, director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber, vividly recalls the standard approach when he entered the field in the 1970s.

“If a patient came into the clinic with a breast lump, she’d be admitted to the hospital where she’d sign a consent form permitting the surgeon to do a radical mastectomy if the lump was found to be cancerous,” he reflects. “She would wake up

from anesthesia to find her breast and part of her chest wall had been removed. The complications – musculoskeletal damage, painful buildups of lymph fluid in nearby tissues, restrictions on movement – could be severe.”

The reason for such disfiguring procedures was not just an excess of caution against cancer spread, but a fundamentally mistaken understanding of the nature of breast cancer, Dr. Iglehart continues. “Back then, we were taught that breast cancer begins in the breast and spreads through the lymph nodes to the rest of the body. Now, we know this is not true. Tumors that arise in the breast may spread to the lymph nodes, but they may also spread through the bloodstream, both routes, or not at all. The key is to determine which type of breast cancer a woman has – by looking at the genetic make-up of the tumor cells and other factors – and treat it accordingly.”

One Size Does Not Fit AllThe trend away from near-universal mastectomies began

with demands from patients for less-deforming procedures, and accelerated with scientific discoveries that changed scientists’ understanding of how breast cancer cells behave. Physicians began studying breast-conserving techniques in the 1980s to see if they were advisable for some patients. When clinical trials showed that lumpectomy followed by precision radiation therapy was just as effective against breast tumors as mastectomy, a critical corner was turned.

Today, Dr. Iglehart remarks, most operations for breast tumors are done on an outpatient basis, with patients going home within hours of the procedure. He estimates that he does a tenth as many mastectomies today as when he began his career.

The shift toward conservation is also evident in surgical


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approaches to the lymph nodes leading from the breast. Instead of removing nearly all of the nodes under the arm and near the collarbone – as was once routine – surgeons now check a few lymph nodes closest to the tumor for cancer cells. If these “sentinel” nodes are clear, the cancer is unlikely to have entered the lymph system, and no further nodes are removed.

Even if cancer cells are found in the sentinel nodes, addi-tional nodes are no longer automatically removed. Depending on the patient and the type of breast cancer involved, doctors may recommend another treatment – hormonal therapy, chemotherapy, or radiation therapy – that is equally or more effective, but far more sparing of a patient’s tissue.

“The fact that we no longer routinely remove lymph nodes from the underarm area is one of the most notable improvements in breast cancer surgery in the past 15 to 20 years,” says Eric Winer, MD, the director of the Breast Oncology Center at Dana-Farber. “Recent studies have shown the advantages, in many cases, of treatments that involve less surgery in these patients.”

As Dr. Winer notes, the removal of these nodes can produce significant physical problems. The most common is

lymphedema, an accumulation of lymph fluid that leads to swelling in the arm,

hand, chest, or back. The result can be throbbing pain and restricted motion in the arm and shoulder.

Other advances have made it possible for women who might oth-

erwise need a mastectomy to receive a lumpectomy, instead. “There are

now pre-treatment options that can shrink tumors in some women prior to surgery, so a more limited procedure can be performed,”

Dr. Winer explains. Improved imaging technologies help phy-sicians determine which patients are the best candidates for conservative surgeries.

Quantity and QualityThe most surprising aspect of these changes is that tissue-

sparing procedures can increase not only the quality but also the length of patients’ lives.

Much of the improvement in survival rates in the past 35 years is due to earlier detection of the disease, better sys-temic agents and combinations, and targeted drugs that single out cancer cells for destruction. But advances in the “local” management of breast cancer – treatments directed within the breast itself – have played a critical role as well. In this respect, it’s fair to say that a minimalist approach with respect to surgery and radiation have had a maximal effect.

Indeed, radiation therapy has followed the same trajec-tory as surgery over the past decade, evolving a more limited, tissue-preserving approach and healthier, longer-living patients.

Jay Harris, MD, chair of Radiation Oncology at Dana-Farber, points to several areas where precision techniques

1 www.dana-farber.org

Eric Winer, MD, shown with his patient, Martha Horn, explains that treating breast cancer before surgery can shrink the tumor enough to allow a more limited procedure.

Turning Point 01

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are yielding improved results. New types of imaging provide crisper, more detailed pictures of breast tumors, enabling sur-geons and radiation therapists to target breast tumors more accurately and cause as little damage to surrounding tissue as possible. Imaging also helps guide daily treatment to ensure greater accuracy.

In addition, system-wide adjuvant therapy – chemo-therapy and hormonal therapy that reduce the chances that a cancer will recur at distant sites – interacts in beneficial ways with radiation therapy. One study found that patients who underwent surgery for a particular type of breast cancer and then received radiation and adjuvant chemotherapy had a cancer-recurrence rate of only 3 percent, compared to 10 percent in patients who didn’t receive chemotherapy – a two-thirds reduction.

Recent news is even better. “For many years, it had been thought that lumpectomy followed by radiation therapy reduced the chances of local recurrence but would have no effect on how long patients survive,” Dr. Harris states. “But a meta-analysis – a study that analyzed the combined results of many other studies – showed that radiation therapy after


surgery results in a major improvement in long-term survival rates. For every four local recurrences avoided, there is one additional survivor five years after treatment.”

Along with improved efficiency has come a renewed emphasis on safety. “Some of these advances have come from improvements in radiation therapy equipment and software, which enable us to provide an optimal dose to the treatment area while avoiding nearby, healthy tissue,” Dr. Harris observes.

A new technique for sparing normal tissue is as low-tech as can be imagined. Traditional approaches to irradiating breast tumors have sometimes resulted in cardiac problems because of radiation penetrating to the heart. Doctors have known for years that holding one’s breath causes the heart to become nar-rower. Dr. Harris wrote the first paper suggesting that having patients hold a deep breath while receiving radiation therapy could greatly reduce the amount of radiation reaching the heart.

Today, the “deep inspiration breath-hold” technique is standard practice around the world. At Dana-Farber, techni-cians use a sophisticated imaging system to ensure patients’ breath holds are consistent during each treatment.

Breast cancer patient Dian Burhoe (left) has benefited from tissue-sparing radiation treatments recommended by her radiation oncologist Jay Harris, MD (right).

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by Scott P. Edwards


Eileen Duffey-Lind, RN, MSN, Eileen Duffey-Lind, RN, MSN, a pediatric nurse at Dana-Farber, a pediatric nurse at Dana-Farber, honors her sister, Maureen.honors her sister, Maureen.

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Despite seeing the effects of cancer on a daily basis, Eileen Duffey-Lind, RN, MSN, a pediatric

nurse practitioner at Dana-Farber, was unprepared when her sister, Maureen, was diagnosed with cervical cancer in 2003. After treatment, Maureen’s cancer remained in remission for three years before it came back with a vengeance. The aggressive disease and intolerable side effects of an investiga-tional drug took their toll, and Mau-reen died in December 2006, at age 37.

“Because I deal with cancer on a regu-lar basis, I thought I could handle any-thing that came my way when my sister was diagnosed,” writes Duffey-Lind on the website for Team Maureen, the fund-raising and support vehicle she established as a promise to keep Maureen’s spirit alive. “Yet I soon realized that nothing could be further from the truth. Because of her cancer diagnosis, I was given the opportunity to see things through the patient’s eyes, not just the provider’s.”

Money raised by Team Maureen, through the Pan-Massachusetts Chal-lenge bike-a-thon and other activities, supports research on cervical cancer

at Dana-Farber. Research directed by Ursula Matulonis, MD, medical director of Gynecologic Oncology at Dana-Farber and Maureen’s doctor, is aimed at better understanding the molecular mutations that drive cervical cancer, and identifying new therapeutic approaches for patients with few treatment options once the cancer has recurred.

Although cervical and endometrial cancers often don’t receive the attention that breast cancer does, Dr. Matulonis considers them “extremely impor-tant cancers” that affect thousands of women worldwide. Endometrial cancer, which forms in the lining of the uterus, is the most prevalent gynecologic malig-nancy in the U.S. (twice as common as ovarian cancer). Cervical cancer, a slow-forming malignancy, is the second most common women’s cancer killer in the world after breast cancer, especially among women in developing countries.

Early detection, either through screening with Pap tests (in the case of cervical cancer) or paying attention to warning signs such as abnormal vaginal bleeding or spotting (for endometrial cancer), means that many of these cancers are found at an early stage when treatment is more effective.

There is increasing emphasis at Dana-Farber, however, on research and treatment of endometrial and cervical cancers, particularly at advanced stages, says Dr. Matulonis.

Disrupting SignalsDisrupting SignalsAndrea Myers, MD, PhD, a medical

oncologist at Dana-Farber, directs clini-cal trials of drugs that target mutations driving the development of endometrial cancer. One, a multicenter phase II trial funded through a “Stand Up To Cancer” grant, is examining genetic mutations that result in the activation of the PI3K signaling pathway, which promotes the uncontrolled cell growth powering tumor development.

Endometrial cancer has one of the highest rates of genetic mutations in the PI3K pathway. A common mechanism of PI3K activation occurs when a tumor suppressor called PTEN (phosphatase and tensin homolog) and a PI3K sub-unit, which is encoded by the cancer-causing PI3KCA gene, are silenced. In addition, studies have shown that the activity of the PI3KCA gene is cranked up like the volume of a teenager’s iPod in the most aggressive forms of endo-metrial cancer. PI3K also interacts


Silencing the Signals Scientists find pathways that control cell growth in Scientists find pathways that control cell growth in

endometrial and cervical cancerendometrial and cervical cancer

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with another important cancer-growth pathway, called RAS-ERK. Many experts feel that this interaction may foster drug resistance and render treat-ment unsuccessful.

The Myers trial enrolls women with advanced, recurrent, or persistent endometrial cancer and treats them with MK-2206, an investigational drug that affects an important component of the PI3K signaling pathway called “akt” that promotes cell survival. Tissue samples are collected from patients and examined via high-throughput genetic analysis during the course of treatment to determine the presence or absence of mutations that lead to PI3K activation. The researchers will use this genetic information to assess patients’ response to MK-2206.

“We hope to use information about the genetics of patients’ tumors to assess their response to certain targeted drugs,” says Dr. Myers. “As such, treatments can be optimized to each patient in the safest and most effective way possible.”

Finding Options for a Finding Options for a ‘Forgotten’ Disease‘Forgotten’ Disease

While the standard treatments for cervical cancer – surgery, pelvic radiation, and chemotherapy – can be effective, very few new options have been developed in nearly a decade.

Dana-Farber physician-scientist Alexi Wright, MD, studies the genetic mutations of cervical cancer. She is currently taking tissue samples from 70 patients at all stages of disease,

including adenocarcinomas (a more aggressive form of the disease, which can be missed on Pap smears) and squamous cell carcinomas (which account for the vast majority of cases), to determine if there are common or different mutations across these subtypes. Her team used a mass spectrometry tool called OncoMap, developed at Dana-Farber, to analyze the genetic makeup of cancer cells and ferret out mutations in tumor DNA for which targeted therapies already exist or are in development.

So far, Dr. Wright and her colleagues discovered that 34 percent of the cancers they analyzed had mutations in the PI3K pathway, the same signaling pathway being studied by Dr. Myers. They also found distinct mutations in squamous cell carcinomas and adenocarcinomas, suggesting different therapeutic rationales for each subtype.

This is one of the largest groups of cervical cancer tumor samples studied to date, and the findings suggest that targeted therapies tailored to the tumor type, rather than more generalized approaches, may be more effective than existing therapies. PI3K inhibitors are currently in clinical trials, mostly

for endometrial cancer, but are now beginning in cervical cancer, as well. Dr. Wright presents her research at the 2012 meeting of the American Society of Clinical Oncology.

“This research inspires me,” says Dr. Wright, “because a lot of people seem to think that cervical cancer has been taken care of in the U.S. due to Pap smears that provide early detection and the human papillomavirus vaccine that offers prevention. It’s almost as if it’s become a forgotten disease. But each patient diagnosed with cervical cancer desperately needs options.”

A better molecular understanding of cancer has yielded new discoveries, summarizes Dr. Matulonis, but to date there has been little research investigating the genetic drivers in gynecologic cancers. Dana-Farber has made a concerted effort to get patients into selected phase I clinical trials of new targeted therapies, and several trials have gone on to phase II because of patients’ responses.

“The incidence of endometrial cancer is rising in the U.S.,” she says. “And cervical cancer is a major health problem worldwide, especially in developing countries. It is our mission at Dana-Farber to make a difference.”

A gene-scanning tool known as A gene-scanning tool known as OncoMap has made it possible to OncoMap has made it possible to study the genetic mutations behind study the genetic mutations behind endometrial and cervical cancer. Mark endometrial and cervical cancer. Mark Byrne, a technologist at Brigham and Byrne, a technologist at Brigham and Women’s Hospital, prepares samples Women’s Hospital, prepares samples of tumor tissue for analysis.of tumor tissue for analysis.

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At a time when collaborations among cancer investigators often span countries and continents, is there any

benefit to having potential research partners right next door? In a word, absolutely.

When Dana-Farber decided to build a new cancer care center alongside a scientific research building, the hope was that proximity would spur collegiality; basic scientists and their clinical investigator neighbors would find new oppor-tunities to work together. The result would be a direct con-nection between the laboratories where new therapies are discovered and the clinics where they’re studied in patients.

In the year since the opening of Dana-Farber’s Yawkey Center for Cancer Care – home to the Institute’s adult treat-ment areas and clinics – this goal has been met many times over. Research that bridges the once “great divide” between laboratory experiment and clinical treatment is gathering momentum throughout the Institute.

The Susan F. Smith Center for Women’s Cancers is a prime example. From clinics on the ninth and 10th floors of the Yawkey Center, the center’s specialists in breast and

gynecologic cancers are involved in dozens of research proj-ects, collaborating with lab-based scientists a short walk away.

“We were determined that the bridges connecting the Yawkey Center to the Richard A. and Susan F. Smith Research Laboratories not be just a symbol, but a real cross-roads for scientists from different disciplines and specialties,” says J. Dirk Iglehart, MD, the Smith Center’s director. “All evidence indicates they have become just that.”

As Dr. Iglehart is the first to note, proximity alone is not enough to encourage basic and clinical scientists to work together. But when the potential research partners next door are leaders in their fields, the opportunity is too inviting to pass up. In some cases, scientists have chosen to pursue a particular line of research precisely because it offered a chance to work with a fellow Dana-Farber investigator.

by Robert Levy


Bridges & PartnershipsSpeeding Discovery from Lab to Clinic

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Examples of bench-to-bedside research abound in the Susan F. Smith Center for Women’s Cancers.

Testing New Compounds for HER2-Positive Breast CancerLike a character in Charles Dickens’ novel Oliver Twist,

cancer is an Artful Dodger, able to slip past many of the impediments that medicine puts in its way.

A prime example is HER2-positive breast cancers, named for a protein that saturates its surface. The drug trastuzumab – better known as Herceptin – has become a staple for treating such cancers. By blocking HER2, it disrupts the signals involved in cell division, halting or reversing tumor growth. Often, however, the tumor cells improvise a comeback by activating signal transmission lines that work independently of HER2.

Dana-Farber’s Jean Zhao, PhD, has demonstrated that proteins known as PI3 kinases play a key role in these alternate circuits. Researchers have begun to explore whether drugs that target those kinases can offer a useful therapy for cancers with an activation of the PI3 kinase pathway.

The search for such drugs narrowed when Dr. Zhao found that one variety, or “isoform,” of PI3 kinase plays an outsized role in cancer cell growth and proliferation. “Drugs that inhibit that one isoform – known as p110α – may be the most effective at blocking PI3 kinase activity,” says Dr. Zhao, whose Dana-Farber collaborators include Thomas Roberts, PhD.

Taking a cue from Dr. Zhao’s work, Eric Winer, MD, director of Dana-Farber’s Breast Oncology Center, along with colleagues Ian Krop, MD, PhD, and Nancy Lin, MD, are organizing a clinical trial of compounds that specifically attack the p110α isoform. “Our goal is to find new approaches to treat resistant HER2-positive cancers,” Dr. Winer states. “We recognize that one treatment will not work for all patients, but this approach may be highly effective for some women.”

Endometrial Cancer GeneticsAnother research duo is taking aim at

the most common gynecologic malignancy in the U.S. – endometrial cancer, a growth in the lining of the uterus that affects 40,000 women in the U.S. every year. (See related article on page 14.)

Little is known about the molecular mishaps that trigger and sustain endometrial cancer, but investigators at Dana-Farber are trying to solve these mysteries. Jean Zhao, PhD, is creating genetically engineered mice to model the development of endometrial tumors. She has already found that when the

mice have mutations in certain tumor-suppressing or tumor-causing genes, a molecular pathway known as the PI3-kinase/mTOR pathway becomes overactive in endometrial tissue. These events produce highly invasive tumors that mirror the characteristics of advanced uterine cancers in humans.

“Endometrial tumors contain many mutations, but they cluster in the PI3-kinase pathway,” Dr. Zhao remarks. “Targeting that pathway is a key to treatment.”

In conjunction with Dr. Zhao’s work, Andrea Myers, MD, PhD, is leading a

multi-center clinical trial of a targeted therapy in women whose endometrial tumors have PI3-kinase mutations. The drug works by inhibiting a key element in the PI3-kinase pathway. Preliminary results of the study are expected to be ready later this year.

“As part of the research, we’ll be analyzing tissue from trial participants to determine the molecular characteristics of the tumors that respond best to the drug,” Dr. Myers comments. “This is one step in matching treatments to patients who can derive the most benefit from them.”


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Bridges Near and FarOne of the United States’ most valuable exports is

the expertise of physicians and researchers who come

here to work and study, then bring their knowledge

and skills back to their own countries. The benefits

flow not only overseas but also to the American clinics

and labs where the visitors train: Sharing ideas and

techniques can educate everyone involved.

The Susan F. Smith Center for Women’s Cancers has

several programs that create this kind of exchange. An

international fellowship program brings breast cancer

physician-scientists to Dana-Farber for two years of

clinical work and research. Launched in 2010, the

program has hosted fellows from Australia, Brazil, and

Portugal, says Eric Winer, MD, director of Dana-Farber’s

Breast Oncology Center.

“Our hope is that they learn from us just as we learn

from them,” Dr. Winer remarks. “They have an oppor-

tunity to see how we work clinically and to engage in

short-term research, and when they return to their own

countries, they can continue to collaborate with us.”

Another program is geared to the individual inter-

ests and schedules of foreign breast cancer surgeons.

“We can tailor the program to the time physicians have

available – whether a week or a year – and address

what they hope to learn,” says Mehra Golshan, MD,

director of Breast Surgical Services. “They may be in the

middle of their medical residencies, or in practice, or

changing specialties. They may be interested in surgical

oncology, medical oncology, or imaging. The program is

flexible enough for a variety of situations.”

Most of the participants have been young – fresh

out of specialty training or junior faculty members.

However, a recent participant was a general surgeon in

her 60s who was switching to a specialty in breast sur-

gery and setting up a clinic in her home city in India.

Occasionally, Dana-Farber breast specialists have

a chance to visit the program’s “graduates” in their

home countries, as Dr. Golshan did recently when he

observed a fellow breast surgeon in Taiwan.


Jean Zhao, PhD, and Andrea Myers, MD, PhD; Kornelia Polyak, MD, PhD, and Nancy Lin, MD; and Eric Winer, MD, and Thomas Roberts, PhD, are among the scientist/clinician pairs in the SSC.

Triple-Negative Breast TumorsBy its very name, triple-negative breast cancer suggests a

particularly obstinate form of disease. Although chemotherapy is often effective in this type of tumor, the cancerous cells lack three molecules that might make them vulnerable to more advanced, targeted treatments.

Research by Dana-Farber’s Kornelia Polyak, MD, PhD, has revealed, however, that this once inscrutable type of breast cancer in fact harbors several very promising molecular targets for drug therapy. A soon-to-be-opened trial led by her colleague Nancy Lin, MD, clinical director of the Breast Oncology Center, is examining whether a drug that hits one of those targets is effective in patients with the disease.

Last year, Dr. Polyak and her colleagues reported that many of the cells within triple-negative breast tumors have an overactive network of genes known as the Jak2/Stat3pathway. When the investigators tested compounds that block those genes – first in laboratory samples of triple-negative breast cancer cells, then in mice with the disease – tumor growth halted.

The success of these experiments led Dr. Polyak to contact Dr. Lin, who leads clinical trials of novel breast cancer drugs. “Pharmaceutical companies have been developing drugs that inhibit the Jak2 pathway because the same set of genes is involved in blood malignancies such as leukemia,” Dr. Polyak comments. “We discovered several pathways that seem to drive triple-negative cancers; we decided to focus first on Jak2 because of the existence of drugs that could be tested in clinical trials.”

The trial is the first to study whether a drug that targets the Jak2 pathway can benefit breast cancer patients, Dr. Lin says. “If it succeeds, we’ll begin thinking of ways to combine it with other drugs for maximum effectiveness.”

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Survivor Spotlight

On her first day as a Dana-Farber patient,

Margaret Winchester had a chance

encounter that helped set the tone for her

ovarian cancer journey.

Passionate about AdvocacyAttorney chooses Dana-Farber for advanced therapies

by Debra Bradley Ruder

She had just met with surgical oncologist Ross Berkowitz, MD, of the Susan F. Smith Center for Women’s Cancers (SSC), and stepped into the ladies’ room. A woman inside commented on the unusually long wait to see her physician that day. “I’m probably the reason you had to wait,” Winchester replied. “Today’s my first time here.

“We had a cry together, and she told me a little about her cancer experience,” Winchester recalls. “It helped

ease my anxiety.”That kind of support

and compassion, com-bined with the Institute’s cutting-edge approach to

cancer care and research, compelled Winchester to

choose Dana-Farber after she was diag-nosed with advanced (stage IIIC) ovarian cancer in 2008.

A 58-year-old child welfare lawyer

from Leominster, Mass., Winchester started her treatment with surgery, con-

ducted by Dr. Berkowitz and his team at Dana-Farber/Brigham and Women’s Cancer Center. They removed her ovaries,

uterus, and as much tumor as possible from her abdomen, where the cancer had spread.

After weighing treatment options with Ursula Matulonis, MD, medical director of Gynecologic Oncology in the SSC, Winchester joined a clinical trial. It involved taking three drugs – carboplatin and paclitaxel delivered directly to her abdomen, and bevacizumab given through a vein. Since then, Winchester’s doctors have used a technique called cryoablation to freeze some small ovarian tumors that have recurred, and she recently began another clinical trial.

Says Dr. Matulonis, “We are so grateful for women like Margaret who take part in clinical trials; they are critical in helping us develop new treatments that are targeted against ovarian cancer and other gynecologic cancers.”

Winchester’s husband, Norman – a retired reserve police officer – was dealing with a recurrence of squamous cell car-cinoma on his ear while his wife was in treatment. He now receives care at Dana-Farber, too.

Acupuncture and a support group have helped Margaret Winchester cope with the physical and emotional effects of her disease. But continuing her work as Managing Attorney of the Children and Family Law Program of the Committee for Public Counsel Services in Worcester, Mass., has been a “saving grace,” she says. “Working gives me a sense of normalcy and focus, even if I’m more tired than before. It helps me stop wor-rying about every ache or pain, accept this as a chronic illness, and try to go on with my life.”

She is also intent on raising awareness about ovarian cancer, considered a silent cancer because it’s frequently not caught until an advanced stage. Her gynecologist had attributed her symptoms of bloating, constipation, and menstrual changes to normal menopause or aging, but after Winchester felt a pain in her side while doing Pilates, her primary-care physician ordered a CT scan that showed a mass.

“Women who have symptoms should ask their doctors for tests,” urges Winchester, who has distributed bookmarks with ovarian cancer warning signs. “Listen to your body. Maybe it’s nothing, and if so, that’s great. But if it’s ovarian cancer, the earlier you catch it, the better.”


Margaret Winchester with her husband, Norman.

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Survivor Spotlight

When Pam Zwemer turned 50 in

2008, she listed 50 things she

wanted to try in her milestone year. Among

them were ride a helicopter, taste the Japanese

beverage sake, and attend a political rally.

A Real Lesson Plan Virginia educator Pam Zwemer turns to Dana-Farber for what’s new in research

by Debra Bradley Ruder

Definitely not on her wish list: Discover that her breast cancer, in remission for several years, had spread to her bones. “For me, 2008 was a kick in the gut,” recalls Zwemer, a high-school math teacher from Chesapeake, Va.

Her oncologist suggested a consultation with Eric Winer, MD, director of the Breast Oncology Center in the Susan F. Smith Center for Women’s Cancers, and she chose to stay in contact with Dana-Farber. She began traveling to the Institute every six months for checkups and went back on tamoxifen, a drug she had taken for five years after her treatment for breast cancer in 2000. Things seemed to be going well.

But when news came last year that cancer cells had migrated to her stomach lining, Zwemer joined a clinical trial under Dr. Winer’s care. It is exploring the side effects of two oral medications, letrozole (a hormonal therapy that reduces estrogen production) and BKM120, thought to overcome the cancer’s resistance to hormonal therapy.

“I feel so blessed to be coming to Dana-Farber,” Zwemer says. “Whatever new research comes out, I feel I’ll be right there for it.”

Zwemer’s treatment schedule reflects her dedication to her students at Oscar Smith High School in Chesapeake, where she chairs the math department and teaches geometry, statis-tics, and other subjects. She typically travels to Boston once a month on Wednesday afternoons. She sees her care team on Thursday and flies home that night so she can teach on Friday. “I try to be a role model for my students,” she says. “Having stage IV breast cancer is only part of my identity. I’m still me.”

Determined to help in some way, her school community hosted a spaghetti supper that raised more than $9,000 for Zwemer’s travel expenses. Her lodging in Boston is free (and fun) because she stays with her son, a medical resident at Children’s Hospital Boston, and daughter-in-law, who live near Dana-Farber.

Zwemer marvels at Dr. Winer’s approach. “He connects incredibly well with people,” she comments. “I feel comforted by his presence; when he smiles, I know I’m in good hands.” Dr. Winer coordinates with Zwemer’s oncologist in Virginia, Michael E. Lee, MD. “Regular communication between a patient’s referring doctor and our team is critical,” Dr. Winer says. “It leads to the best care for the patient, and it enhances the referring doctor’s practice and our own.”

Zwemer remembers emailing Dr. Winer the night she learned the cancer had invaded her stomach, and how they exchanged mes-sages about next steps. “At 10:30 p.m., there he was on my screen,” she recalls, choking up. “That touched me.”

Knowing about treatment options reassures Zwemer, who carries a white binder filled with test results, appointment notes, and care-givers’ business cards. She says she is the kind of person who needs a plan, and having one feels good.


Pam Zwemer, carrying the white binder she uses to keep track of test results and other details.

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Non-profit Org.U.S. PostageP A I D

Dana-Farber

Dana-Farber Cancer Institute450 Brookline AvenueBoston, MA 02215617-632-4090www.dana-farber.org

A teaching affiliate of

Harvard Medical School

Individuals — $9,494,433

Foundations — $2,549,650

Events — $2,136,063

Corporations — $816,358

17%

14%

5%

64%

Making a DifferenceA Legacy of Support

Thanks to the ongoing generosity of its donors, Dana-Farber’s Susan F. Smith Center for Women’s Cancers has raised more than $98 million over the past 13 years, and nearly $15 million in fiscal year 2011 alone.

To learn more about how you can strengthen our ongoingwork against women’s cancers, contact Katherine Raute at 617-632-6550 or [email protected].

The American Cancer Society estimates that in 2011 more than a quarter million women were diagnosed with breast or gynecological cancers; more than 69,000 lost their lives to these diseases. Thanks to the vision and generosity of our donors, Dana-Farber continues to offer patients the best in care while pursuing research that will lead to more effectiveand less toxic treatments. Our scientists continue to make progress on many fronts in their ongoing battle against these complex diseases. There are many ways in which patients, families, and friends can contribute as well.

Other Ways to HelpDonating blood or platelets can help a diverse range of

patients at Dana-Farber and Brigham and Women’s Hospital. For information on how to donate, visit www.danafarber.org/blooddonation or call 888-LETSGIV (888-538-7448).

To learn more about becoming a potential bone marrow/stem cell donor, visit www.dana-farber.org/nmdp or call Dana-Farber’s National Marrow Donor Program Donor office at 617-632-2561 or 866-875-3324.

To make a gift from your smartphone, scan this QR code. Or visit www.dana-farber.org/gift. You’ll be directed to our “Make A Gift” donation page.

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