breast cancer treatment, outcomes and recent...
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Breast Cancer Treatment, Outcomes and
Recent Advances
Ogori N Kalu, MD, MS
Director Breast Surgery-UH
Asst. Prof of Surgery
Rutgers NJ Med School
National Statistics
1 in 8 women in the U.S. (12 - 13%) will develop invasive breast cancer over the course of her lifetime.
In 2010, an estimated 207,000 new cases of invasive breast
cancer were diagnosed in women in the U.S., along with 54,000 new cases of non-invasive (in situ) breast cancer; and an estimated 40,000 cancer related deaths were reported.
About 1,970 new cases of invasive breast cancer were
diagnosed in men in 2010. Less than 1% of all new breast cancer cases occur in men
Among women aged 20-59 years, breast cancer remains the
leading cause of cancer death despite a steady decrease in breast cancer mortality since 1990.
Cancer
Site
NJ
2006-
2010
US
2006-
2010
BREAST All
Races
White Black API Hispanic All
Races
White Black API Hispa
nic
Incidence 129.3 133.6 117.1 86. 91.8 122.2 123.5 118 84.7 91.1
Mortality 25.2 25.1 30.9 11.7 13.2 22.6 22.1 30.8 11.5 14.8
COMPARATIVE INCIDENCE & MORTALITY RATES,
NJ and US, FEMALES, 2006-2010
(NAACCR-age-adjusted rates per 100,000 (2000 US population standard))
Distribution of Stage at Diagnosis of Breast Cancer,
Females, 2006-2010
ALL RACES WHITE BLACK API HISPANIC*
BREAST
Total Cases 44,430 37,017 4,895 2,097 3,374
Percent 100% 100% 100% 100% 100%
In Situ 23.4% 23.5% 20.3% 27.9% 23.6%
Local 46.5% 47.7% 40.8% 41.3% 43.0%
Regional 22.6% 21.8% 28.8% 24.0% 26.4%
Distant 4.7% 4.5% 6.6% 4.1% 4.5%
Unstaged 2.7% 2.5% 3.6% 2.8% 2.6%
Trends in Female Breast Cancer Incidence and Death Rates by Race and Ethnicity, United States.
Rates are age-adjusted to the 2000 US Standard Population.
Data are from the SEER Cancer Statistics Review, 1975-2005, National Cancer Institute, Bethesda, MD.4
From Huo and Dignam in Kuerer’s Breast Surgical Oncology, 2010.
Does Cancer Health Disparity = Health Care
Disparity?
Income and education influence health insurance coverage and access to appropriate early detection, treatment and palliative care
Socioeconomic factors influence exposure to cancer risk factors: tobacco use, poor nutrition, physical activity, and obesity
Cultural factors influence health behavior, attitudes toward disease, and choice of treatment
Socioeconomic Factors and Access to Medical Care:
Are they the only Factors?
Socioeconomic factors account for stage differences at diagnosis for most cancers but not breast and prostate cancer (Cancer 2002, 94: 2844 - 2854; Cancer Causes and Control 2003, 14: 761 - 766)
Traditional socioeconomic, clinical, and pathologic factors do not account for the race-related stage difference at diagnosis for prostate cancer (JNCI 2001, 93: 388 - 395)
Breast cancer survival differs by race (AA versus EA) in an equal-access
health care facility (Cancer 1998, 82: 1310 - 1318; Cancer 2003, 98: 894 - 899)
Accounting for traditional risk factors explains differences in breast cancer incidence and outcome for all race/ethnic groups except African Americans (JNCI 2005, 97: 439 - 448)
Being insured and having access to medical care does not eliminate the survival disparity for African American women with breast cancer (JNCI Monogr 2005, 35: 88 - 95)
What about biology??
“While data suggest that access to
quality care is a factor in cancer
disparities, other factors also play a
major role, including tumor biology and
genetics”
(JNCI 2009, 101: 984
– 92)
Biology and Cancer Health Disparity
Race/ethnic disparity in prevalence of basal-like breast tumors (JAMA 2006, 295: 2492 – 2502)
Most common among young women of African descent
Caveat: Breast cancer survival disparity in US is irrespective of tumor ER status (JNCI 2009, 101: 993 – 1000)
High proportion of breast cancer patients in West Africa
present with high grade and triple negative disease (J Clin Oncol 2009, 27: 4514 – 21)
Race/ethnic differences in prevalence of 8q24 cancer
susceptibility markers (Nat Genet 2007, 39: 638 – 44 & 954 – 6; Genome Res 2007, 17: 1717 – 22)
Risk alleles are more common among African-Americans
Genomic Subtypes
Luminal A: 40%; ER+ and/or PR+; HER2-, slow
growing, least aggressive, best prognosis
Luminal B: 10-20%; ER+ and/or PR+; HER2+ or high
proliferation rate
HER2-enriched: 10%; ER/PR-
Basal-like: 10-20%; ER/PR/Her2-; worst prognosis
Claudin-low: 10%; similar to basal-like
Breast Cancer
Receptors
ER: estrogen
receptor
PR: progesterone
receptor
HER2: human
epidermal growth
factor receptor-2 E2=estrogen
EGF= epidermal
growth factor
Target specific
medications
Trastuzumab
(Herceptin)
AI=aromatase
inhibitors
(anastrozole,
exemestane)
Tamoxifen
Lapatinib
(Tykerb)
Figure 5. Effects of about 5 years of tamoxifen on the 15-year probabilities of recurrence and of
breast cancer mortality, for ER-positive disease Outcome by allocated treatment in trials of about 5
years of adjuvant tamoxifen
Early Breast Cancer Trialists' Collaborative Group (EBCTCG) :
Metaanalysis Tamoxifen Efficacy
The Lancet, Volume 378, Issue 9793, 2011, 771 - 784
Effect of anastrozole and tamoxifen as adjuvant treatment for
early-stage breast cancer: 10-year analysis of the ATAC trial
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial
Compare efficacy and safety of anastrozole (1 mg) with tamoxifen (20 mg), as
adjuvant treatment for postmenopausal women with early-stage ER+ breast cancer.
Anastrazole compared with tamoxifen had improved :
• disease-free survival
• time to recurrence
• time to distant recurrence
• Fewer contralateral breast cancers as first event compared
to tamoxifen daily for 5 years (HR 0.60; 95% CI 0.42-085;
p=0.004)
• Increased arthralgia and bone fractures
Cuzick, et al, The Lancet Oncology, Volume 11, Issue 12, Pages 1135 - 1141, December 2010
Adjuvant Endocrine Therapy
Comparison of
overall survival
by disease
stage for
women with
triple negative
breast cancer
(TNBC) and
those with other
phenotypes
Adapted from Bauer et
al
Who gets triple negative
breast cancer? ANY WOMAN CAN GET TRIPLE NEGATIVE BREAST
CANCER
Highest representation in the following populations:
Women of African descent
Pre-menopausal women
BRCA gene mutation ( BRCA-1)
Younger age at menarche, higher parity, younger
age at full term pregnancy, shorter duration breast
feeding, and higher body mass index (BMI),
especially among pre-menopausal women.
By age 20 1 out of 1,681
By age 30 1 out of 232
By age 40 1 out of 69
By age 50 1 out of 42
By age 60 1 out of 29
By age 70 1 out of 27
Lifetime 1 out of 8
American Cancer Society Breast
Cancer Facts & Figures, 2011-2012.
Probability of Developing Breast Cancer Within the Next 10 years
Age (yrs) In Situ
cases
Invasive
cases
Deaths
< 40 1900 10980 1020
<50 15,650 48,910 4,780
50-64 26,770 84,210 11,970
65+ 22,220 99,220 22,870
All ages 64,640 232,340 39,620
Estimated New Female Breast Cancer Cases and Deaths by Age, US, 2013
Modified from the American Cancer Society,
Surveillance and Health Service Research
2013
Different risk factors
compared to older women
More likely to be associated with an increased
familial risk (BRCA1, BRCA2, TP53, PTEN
mutations)
Obesity, high caloric intake, high alcohol use,
red meat, sedentary lifestyle
Recent OCP use, particularly for ER-negative
tumors
Early childbearing and multiparity
Variations according to race
and ethnicity
Women >45, breast cancer is more common in whites
than blacks
Black women under the age of 35 have 2X the incidence
of invasive breast cancer and 3X the mortality rate than
white women
Young black women with Stages II and IV disease had a
worse prognosis despite standard therapy
(Cancer Causes Control 2003;14:151-60. Cancer 2003:97:134-47)
Su
rviv
al
(%)
Age at Diagnosis (Years)
Five year relative survival of females diagnosed with breast cancer during 2000-
2005, SEER 17
Clinicopathologic Features
Cancers in women<40:
tumors were larger (P=.012)
of higher grade (P=.0001)
more lymph node positivity (P=.008)
lower ER positivity (P=.027)
higher rates of HER2/neu over-expression
(P=.075)
Inferior disease-free survival
(HR=1.32,P=.094)
J Clin Onc 2008;26:3324-30
Treatment: variations in
outcomes Women < 50 treated for breast cancer had
higher rates of second cancers (bone, ovary,
thyroid, kidney)
Women <36 y have 13% 10-year cumulative
incidence of contralateral breast cancer
Women <45 y: Both post lumpectomy and
mastectomy radiation conferred an additional
50% incr risk in contralateral breast ca
Cancer Epidem Biom Prev 2008;17:2647-55
J Clin Oncol 2008;26:5561-8
Considerations
Fertility and pregnancy
Impact of infertility post treatment
Bone health
Bone density loss after treatment; risk of long term
osteopenia, osteoporosis, fractures
Psychosocial issues
Adequate screening and risk assessment
History of Breast Cancer Surgery
1600 BC: Ancient Egyptians treated breast tumors with cauterization via “fire drill”
17/18th century: Jean Louis Petit, French surgeon linked the
concept that cancer spread via lymphatics. First to remove lymph nodes, breast, pectoral muscles
1882: William Stewart Halstead radical mx 1940s: modified radical mastectomy 1971: NSABP B-04: total mx= radical mx 1976: NSABP B-06: lump+ALND+rads=MRM 1999 (2004): NSABP B32: importance of SLNB 2010: ACOSOG Z0011: Futility of ALND for node postive
SLNB, for pts undergoing BCT and systemic therapy
Breast Cancer Treatment
SURGERY BREAST CONSERVATION MASTECTOMY Lumpectomy, partial/segmental Simple/total mastectomy or quadrantectomy Modified radical mastectomy
Contraindicated in RECONSTRUCTION hx of prior radiation Immediate v delayed Size > 4cm; tumor:breast ratio pregnant women who would require radiation while pregnant
Changing Patterns in Surgery
Increasing mastectomy and CPM rates Freedom from imaging surveillance
▪ Imaging Fatigue or “No Mas” Syndrome Availability of better reconstructive
techniques Nipple-sparing mastectomies seemingly
oncologically safe
• removal of NAC is perceived as mutilating
• “…NAC seems to be the signature of the breast identity more than the volume or the shape….” J.Y. Petit 2009
Contralateral Prophylactic Mastectomy Rates
for Invasive and DCIS
Tuttle, T. M. et al. J Clin Oncol; 25:5203-5209 2007
ALL Mastectomy Patients with CPM (Invasive -SEER)
Tuttle, T. M. et al. J Clin Oncol; 27:1362-1367 2009
ALL Mastectomy Patients with CPM (DCIS-SEER)