Treatment of breast Treatment of breast cancercancer

Dr.Syed Alam ZebDr.Syed Alam Zeb

ClassificationClassification Carcinoma, NOS (not otherwise Carcinoma, NOS (not otherwise

specified).specified).

Ductal.Ductal. Intraductal (in situ). Intraductal (in situ). Invasive with predominant Invasive with predominant

intraductal component. intraductal component. Invasive, NOS. Invasive, NOS. Comedo. Comedo. Inflammatory. Inflammatory. Medullary with lymphocytic Medullary with lymphocytic

infiltrate. infiltrate. Mucinous (colloid). Mucinous (colloid). Papillary. Papillary. Scirrhous. Scirrhous. Tubular. Tubular. Other. Other.

Lobular.Lobular. In situ. In situ. Invasive with predominant in situ Invasive with predominant in situ

component. component. Invasive.Invasive.

Nipple. Nipple. Paget’s disease, NOS. Paget’s disease, NOS. Paget’s disease with intraductal Paget’s disease with intraductal

carcinoma. carcinoma. Paget’s disease with invasive Paget’s disease with invasive

ductal carcinoma. ductal carcinoma.

Other. Other. Undifferentiated carcinomaUndifferentiated carcinoma..

StagingStaging TX: Primary tumor cannot be TX: Primary tumor cannot be

assessed assessed

T0: No evidence of primary tumor T0: No evidence of primary tumor

Tis: Intraductal carcinoma, lobular Tis: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s carcinoma in situ, or Paget’s disease of the nipple with no disease of the nipple with no associated invasion of normal associated invasion of normal breast tissue breast tissue

Tis (DCIS): Ductal carcinoma in Tis (DCIS): Ductal carcinoma in situ situ

Tis (LCIS): Lobular carcinoma in Tis (LCIS): Lobular carcinoma in situ situ

Tis (Paget's): Paget's disease of Tis (Paget's): Paget's disease of the nipple with no tumor.  [the nipple with no tumor.  [Note: Note: Paget's disease associated with a Paget's disease associated with a tumor is classified according to tumor is classified according to the size of the tumor.the size of the tumor.]]

T1: Tumor ≤2.0 cm in greatest T1: Tumor ≤2.0 cm in greatest dimension dimension

T1mic: Microinvasion ≤0.1 cm in T1mic: Microinvasion ≤0.1 cm in greatest dimension greatest dimension

T1a: Tumor >0.1 cm but ≤0.5 cm T1a: Tumor >0.1 cm but ≤0.5 cm in greatest dimension in greatest dimension

T1b: Tumor >0.5 cm but ≤1.0 cm T1b: Tumor >0.5 cm but ≤1.0 cm in greatest dimension in greatest dimension

T1c: Tumor >1.0 cm but ≤2.0 cm T1c: Tumor >1.0 cm but ≤2.0 cm in greatest dimension in greatest dimension

T2: Tumor >2.0 cm but ≤5.0 cm T2: Tumor >2.0 cm but ≤5.0 cm in greatest dimension in greatest dimension

T3: Tumor >5.0 cm in greatest T3: Tumor >5.0 cm in greatest dimensiondimension

Staging (cont)Staging (cont) T4: Tumor of any size with direct extension to T4: Tumor of any size with direct extension to

(a) chest wall or (b) skin, only as described (a) chest wall or (b) skin, only as described below below

T4a: Extension to chest wall, not including T4a: Extension to chest wall, not including pectoralis musclepectoralis muscle

T4b: Edema (including peau d’orange) or T4b: Edema (including peau d’orange) or ulceration of the skin of the breast, or ulceration of the skin of the breast, or satellite skin nodules confined to the same satellite skin nodules confined to the same breast breast

T4c: Both T4a and T4bT4c: Both T4a and T4b

T4d: Inflammatory carcinoma T4d: Inflammatory carcinoma

Regional lymph nodes (N)Regional lymph nodes (N) NX: Regional lymph nodes cannot be NX: Regional lymph nodes cannot be

assessed (e.g., previously removed) assessed (e.g., previously removed)

N0: No regional lymph node metastasis N0: No regional lymph node metastasis

N1: Metastasis to movable ipsilateral axillary N1: Metastasis to movable ipsilateral axillary lymph node(s) lymph node(s)

N2: Metastasis to ipsilateral axillary lymph N2: Metastasis to ipsilateral axillary lymph node(s) fixed or matted, or in clinically node(s) fixed or matted, or in clinically apparent ipsilateral internal mammary nodes apparent ipsilateral internal mammary nodes in the in the absenceabsence of clinically evident lymph of clinically evident lymph node metastasis node metastasis

– N2a: Metastasis in ipsilateral axillary lymph N2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other nodes fixed to one another (matted) or to other structuresstructures

– N2b: Metastasis only in clinically apparent* N2b: Metastasis only in clinically apparent* ipsilateral internal mammary nodes and in the ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node absence of clinically evident axillary lymph node metastasismetastasis

Staging (cont)Staging (cont) N3: Metastasis in ipsilateral N3: Metastasis in ipsilateral

infraclavicular lymph node(s) infraclavicular lymph node(s) with or without axillary lymph with or without axillary lymph node involvement, or in node involvement, or in clinically apparent* ipsilateral clinically apparent* ipsilateral internal mammary lymph internal mammary lymph node(s) and in the node(s) and in the presencepresence of clinically evident axillary of clinically evident axillary lymph node metastasis; or, lymph node metastasis; or, metastasis in ipsilateral metastasis in ipsilateral supraclavicular lymph node(s) supraclavicular lymph node(s) with or without axillary or with or without axillary or internal mammary lymph internal mammary lymph node involvement node involvement

N3a: Metastasis in ipsilateral N3a: Metastasis in ipsilateral infraclavicular lymph node(s)infraclavicular lymph node(s)

N3b: Metastasis in ipsilateral N3b: Metastasis in ipsilateral internal mammary lymph internal mammary lymph node(s) and axillary lymph node(s) and axillary lymph node(s)node(s)

N3c: Metastasis in ipsilateral N3c: Metastasis in ipsilateral supraclavicular lymph node(s)supraclavicular lymph node(s)

Distant metastasis (M) Distant metastasis (M) MX: Presence of distant MX: Presence of distant

metastasis cannot be metastasis cannot be assessed assessed

M0: No distant metastasis M0: No distant metastasis M1: Distant metastasis M1: Distant metastasis

Staging (cont)Staging (cont) Stage 0Stage 0 Tis, N0, M0 Tis, N0, M0 Stage IStage I T1*, N0, M0T1*, N0, M0 Stage IIAStage IIA T0, N1, M0 T0, N1, M0 T1, N1, M0 T1, N1, M0 T2, N0, M0T2, N0, M0 Stage IIBStage IIB T2, N1, M0 T2, N1, M0 T3, N0, M0T3, N0, M0

Stage IIIAStage IIIA T0, N2, M0 T0, N2, M0 T1*, N2, M0 T1*, N2, M0 T2, N2, M0 T2, N2, M0 T3, N1, M0 T3, N1, M0 T3, N2, M0T3, N2, M0 Stage IIIBStage IIIB T4, N0, M0 T4, N0, M0 T4, N1, M0 T4, N1, M0 T4, N2, M0 T4, N2, M0 Stage IIICStage IIIC Any T, N3, M0Any T, N3, M0 Stage IVStage IV Any T, Any N, M1 Any T, Any N, M1

Breast cancer is commonly Breast cancer is commonly treated by various treated by various combinations of:combinations of:

SurgerySurgery radiation therapyradiation therapy chemotherapy, and chemotherapy, and hormone therapy. hormone therapy.

Prognosis and selection of Prognosis and selection of therapy may be influenced by:therapy may be influenced by:

the age and menopausal status the age and menopausal status stage, stage, histologic and nuclear grade of the histologic and nuclear grade of the

primary tumor, primary tumor, estrogen-receptor (ER) and estrogen-receptor (ER) and

progesterone-receptor (PR) status, progesterone-receptor (PR) status, measures of proliferative capacity, and measures of proliferative capacity, and HER2/neu gene amplification.HER2/neu gene amplification.

Since criteria for Since criteria for menopausal status vary menopausal status vary

widely, some studies widely, some studies have substituted age have substituted age

older than 50 years as a older than 50 years as a surrogate for the surrogate for the

postmenopausal state.postmenopausal state.

Patient management following Patient management following initial suspicion of breast initial suspicion of breast

cancer generally includes:cancer generally includes: Confirmation of the diagnosis, Confirmation of the diagnosis, Evaluation of stage of disease, Evaluation of stage of disease, Establishment of unilateral or Establishment of unilateral or

bilateral diseasebilateral disease Selection of therapy. Selection of therapy.

Ductal Carcinoma In SituDuctal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) is a Ductal carcinoma in situ (DCIS) is a noninvasive, precancerous condition. noninvasive, precancerous condition.

DCIS can progress to become invasive DCIS can progress to become invasive cancer, but estimates of the likelihood of cancer, but estimates of the likelihood of this vary widely. this vary widely.

DCIS accounts for about 18% of all newly DCIS accounts for about 18% of all newly diagnosed invasive plus noninvasive diagnosed invasive plus noninvasive breast tumors in the United States. breast tumors in the United States.

Very few cases of DCIS present as a Very few cases of DCIS present as a palpable mass; 80% are diagnosed by palpable mass; 80% are diagnosed by mammography alonemammography alone

Treatment options for DCISTreatment options for DCIS Total mastectomy with or without tamoxifen. Total mastectomy with or without tamoxifen.

Breast-conserving surgery and radiation Breast-conserving surgery and radiation therapy, with or without tamoxifen.therapy, with or without tamoxifen.

Breast-conserving surgery without radiation Breast-conserving surgery without radiation therapy. A large national clinical trial therapy. A large national clinical trial comparing breast-conserving surgery and comparing breast-conserving surgery and tamoxifen with or without radiation therapy is tamoxifen with or without radiation therapy is currently under waycurrently under way

Lobular Carcinoma In SituLobular Carcinoma In Situ

Strictly speaking, it is not known to be a Strictly speaking, it is not known to be a premalignant lesion, but rather a marker premalignant lesion, but rather a marker that identifies women at an increased risk that identifies women at an increased risk for subsequent development of invasive for subsequent development of invasive breast cancer. This risk remains elevated breast cancer. This risk remains elevated even beyond 2 decades, and most of the even beyond 2 decades, and most of the subsequent cancers are ductal rather than subsequent cancers are ductal rather than lobular. lobular.

LCIS is usually multicentric and is LCIS is usually multicentric and is frequently bilateral. frequently bilateral.

Treatment of Lobular Treatment of Lobular Carcinoma In SituCarcinoma In Situ

Most women with LCIS can be managed without Most women with LCIS can be managed without additional local therapy after biopsy. additional local therapy after biopsy.

No evidence is available that re-excision to obtain No evidence is available that re-excision to obtain clear margins is required. clear margins is required.

Tamoxifen has decreased the risk of developing Tamoxifen has decreased the risk of developing breast cancer in women with LCIS and should be breast cancer in women with LCIS and should be considered in the routine management of these considered in the routine management of these womenwomen

Bilateral prophylactic mastectomy is sometimes Bilateral prophylactic mastectomy is sometimes considered an alternative approach for women at considered an alternative approach for women at high risk for breast cancer. high risk for breast cancer.

Axillary lymph node dissection is not necessary.Axillary lymph node dissection is not necessary.

Treatment options for Treatment options for patients with LCISpatients with LCIS

Observation after diagnostic biopsy. Observation after diagnostic biopsy.

Tamoxifen to decrease the incidence of Tamoxifen to decrease the incidence of subsequent breast cancers. subsequent breast cancers.

Ongoing breast cancer prevention trials.Ongoing breast cancer prevention trials.

Bilateral prophylactic total mastectomy, Bilateral prophylactic total mastectomy, without axillary node dissection.without axillary node dissection.

Management of Stage I, II, Management of Stage I, II, IIIA, and Operable IIIC IIIA, and Operable IIIC Breast CancerBreast Cancer Locoregional therapyLocoregional therapy SurgerySurgery Radiation therapyRadiation therapy

Adjuvant therapyAdjuvant therapy Hormonal therapyHormonal therapy ChemotherapyChemotherapy

Locoregional therapyLocoregional therapy

After the presence of a malignancy is confirmed After the presence of a malignancy is confirmed and histology is determined, treatment options and histology is determined, treatment options should be discussed with the patient before a should be discussed with the patient before a therapeutic procedure is selected. therapeutic procedure is selected.

The surgeon may proceed with a definitive The surgeon may proceed with a definitive procedureprocedure

Estrogen-receptor (ER) and progesterone-receptor Estrogen-receptor (ER) and progesterone-receptor (PR) status should be determined for the primary (PR) status should be determined for the primary tumor.Additional pathologic characteristics, tumor.Additional pathologic characteristics, including grade, proliferative activity, and human including grade, proliferative activity, and human epidermal growth factor receptor 2 (HER2/neu) epidermal growth factor receptor 2 (HER2/neu) status, may also be of value.status, may also be of value.

Options for surgical Options for surgical management of the primary management of the primary

tumor include:tumor include: breast-conserving surgery plus breast-conserving surgery plus

radiation therapy,radiation therapy, mastectomy plus reconstruction, and mastectomy plus reconstruction, and mastectomy alone. mastectomy alone.

Selection of a local therapeutic Selection of a local therapeutic approach depends on:approach depends on:

the location of the lesion the location of the lesion size of the lesionsize of the lesion analysis of the mammogramanalysis of the mammogram breast size, and breast size, and the patient’s attitude toward the patient’s attitude toward

preserving the breast. preserving the breast.

relative contraindications to relative contraindications to breast-conserving therapybreast-conserving therapy

The presence of multifocal disease in the The presence of multifocal disease in the breast breast

history of collagen vascular disease.history of collagen vascular disease.

A patient’s age should not be a determining A patient’s age should not be a determining factor in the selection of breast-conserving factor in the selection of breast-conserving treatment versus mastectomy treatment versus mastectomy

Whether young women with germ-line Whether young women with germ-line mutations or strong family histories are mutations or strong family histories are good candidates for breast-conserving good candidates for breast-conserving therapy is not certain. therapy is not certain.

surgical techniques used surgical techniques used include:include:

LumpectomyLumpectomy QuadrantectomyQuadrantectomy segmental mastectomy segmental mastectomy

Which option?Which option?

Patients whose tumors have these Patients whose tumors have these characteristics characteristics

may benefit from a more generous initial may benefit from a more generous initial excision excision

to avoid the need for a re-excision: to avoid the need for a re-excision:

1. large tumors (T2 lesions), 1. large tumors (T2 lesions), 2. positive axillary nodes, 2. positive axillary nodes, 3. extensive intraductal component,3. extensive intraductal component,4. palpable tumors, and 4. palpable tumors, and 5. lobular histology5. lobular histology

Dealing with axillary lymph Dealing with axillary lymph nodesnodes

Axillary node dissection even in the Axillary node dissection even in the presence of clinically negative nodes is a presence of clinically negative nodes is a necessary staging procedure.necessary staging procedure.

Controversy exists as to the extent of the Controversy exists as to the extent of the procedure because of long-term morbidity procedure because of long-term morbidity

The standard evaluation usually involves The standard evaluation usually involves only a level I and II dissection, thereby only a level I and II dissection, thereby removing a satisfactory number of nodes removing a satisfactory number of nodes for evaluation (i.e., 6-10 at a minimum), for evaluation (i.e., 6-10 at a minimum), while reducing morbidity from the while reducing morbidity from the procedure. procedure.

Sentinel lymph node biopsySentinel lymph node biopsy The SLN is defined as the first node in the lymphatic basin that The SLN is defined as the first node in the lymphatic basin that

receives primary lymphatic flow. receives primary lymphatic flow. Studies have shown that the injection of technetium-labeled Studies have shown that the injection of technetium-labeled

sulfur colloid, vital blue dye, or both around the tumor or biopsy sulfur colloid, vital blue dye, or both around the tumor or biopsy cavity, or in the subareolar area, and subsequent drainage of cavity, or in the subareolar area, and subsequent drainage of these compounds to the axilla results in the identification of the these compounds to the axilla results in the identification of the SLN in 92% to 98% of patients SLN in 92% to 98% of patients

These reports demonstrate a 97.5% to 100% concordance These reports demonstrate a 97.5% to 100% concordance between SLN biopsy and complete axillary lymph node between SLN biopsy and complete axillary lymph node dissectiondissection

The results of a randomized trial of 532 patients with T1 The results of a randomized trial of 532 patients with T1 carcinomas undergoing either SLN biopsy plus complete axillary carcinomas undergoing either SLN biopsy plus complete axillary dissection or SLN biopsy alone showed no axillary recurrences in dissection or SLN biopsy alone showed no axillary recurrences in either group and no difference in the 3-year disease-free either group and no difference in the 3-year disease-free survivalsurvival

The reported false-negative rates (i.e., the number of patients The reported false-negative rates (i.e., the number of patients with negative SLN biopsy divided by the number of patients with with negative SLN biopsy divided by the number of patients with positive axillary nodes at the time of axillary node dissection) of positive axillary nodes at the time of axillary node dissection) of SLN biopsy range from 0% to 10%. SLN biopsy range from 0% to 10%.

Radiation therapyRadiation therapy

Following Breast conservationFollowing Breast conservation Following mastectomyFollowing mastectomy

Radiation therapy following Radiation therapy following Breast conservationBreast conservation

Postoperative external-beam radiation therapy to Postoperative external-beam radiation therapy to the entire breast with doses of 45 Gy to 50 Gy, in the entire breast with doses of 45 Gy to 50 Gy, in 1.8 Gy to 2.0 Gy daily fractions over a 5-week 1.8 Gy to 2.0 Gy daily fractions over a 5-week period. period.

Shorter hypofractionation schemes achieve Shorter hypofractionation schemes achieve comparable results.comparable results.

A further radiation boost is commonly given to the A further radiation boost is commonly given to the tumor bed. Two randomized trials conducted in tumor bed. Two randomized trials conducted in Europe have shown that using boosts of 10 Gy to Europe have shown that using boosts of 10 Gy to 16 Gy reduces the risk of local recurrence from 16 Gy reduces the risk of local recurrence from 4.6% to 3.6% at 3 years (4.6% to 3.6% at 3 years (P P = .044),[and from 7.3% = .044),[and from 7.3% to 4.3% at 5 years (to 4.3% at 5 years (PP < .0001), respectively < .0001), respectively

If a boost is used, it can be delivered either by If a boost is used, it can be delivered either by external-beam radiation therapy,or by using an external-beam radiation therapy,or by using an interstitial radioactive implant. interstitial radioactive implant.

Radiation therapy following Radiation therapy following mastectomymastectomy

Postoperative chest wall and regional lymph node adjuvant Postoperative chest wall and regional lymph node adjuvant irradiation is given to selected patients considered at high irradiation is given to selected patients considered at high risk for local-regional failure following mastectomy:risk for local-regional failure following mastectomy:

1.1. Those with 4 or more positive axillary nodesThose with 4 or more positive axillary nodes2.2. Grossly evident extracapsular nodal extensionGrossly evident extracapsular nodal extension3.3. Large primary tumors, and Large primary tumors, and 4.4. Very close or positive deep margins of resection of the Very close or positive deep margins of resection of the

primary tumor.primary tumor. Patients with 1 to 3 involved nodes without any of the Patients with 1 to 3 involved nodes without any of the

previously noted risk factors are at low risk of local previously noted risk factors are at low risk of local recurrence, and the value of routine use of adjuvant recurrence, and the value of routine use of adjuvant radiation therapy is unclear. radiation therapy is unclear.

Adjuvant systemic therapyAdjuvant systemic therapy

Hormone therapyHormone therapy ChemotherapyChemotherapy Monoclonal antibodiesMonoclonal antibodies

Hormone therapyHormone therapy

TamoxifenTamoxifen Aromatase inhibitors: anastrozole, Aromatase inhibitors: anastrozole,

exemestane, letrozoleexemestane, letrozole Ovarian ablationOvarian ablation

TamoxifenTamoxifen

The benefit of tamoxifen was found to be restricted to The benefit of tamoxifen was found to be restricted to women with ER-positive or ER-unknown breast tumors. In women with ER-positive or ER-unknown breast tumors. In these women, the 15-year absolute reductions in these women, the 15-year absolute reductions in recurrence and mortality associated with 5 years of use are recurrence and mortality associated with 5 years of use are 12% and 9%, respectively.12% and 9%, respectively.

Women younger than 50 years obtained a degree of benefit Women younger than 50 years obtained a degree of benefit from 5 years of tamoxifen similar to that obtained by older from 5 years of tamoxifen similar to that obtained by older women. women.

In addition, the proportional reductions in both recurrence In addition, the proportional reductions in both recurrence and mortality associated with tamoxifen use were similar in and mortality associated with tamoxifen use were similar in women with either node-negative or node-positive breast women with either node-negative or node-positive breast cancer, but the absolute improvement in survival at 10 cancer, but the absolute improvement in survival at 10 years was greater in the latter group (5.3% vs. 12.5% with years was greater in the latter group (5.3% vs. 12.5% with 5 years of use) 5 years of use)

The current recommendation is that adjuvant tamoxifen be The current recommendation is that adjuvant tamoxifen be discontinued after 5 years in all patients as current discontinued after 5 years in all patients as current standard therapy. standard therapy.

Tamoxifen toxic effectsTamoxifen toxic effects

Endometrial cancerEndometrial cancer Increased incidence of deep venous Increased incidence of deep venous

thrombosis and pulmonary emboli. thrombosis and pulmonary emboli. Benign ovarian cysts Benign ovarian cysts Visual problems Visual problems

Aromatase inhibitors: Aromatase inhibitors: anastrozoleanastrozole

Patients on anastrozole have a Patients on anastrozole have a significantly longer disease-free significantly longer disease-free survival than those on tamoxifen.survival than those on tamoxifen.

Aromatase inhibitors: Aromatase inhibitors: exemestaneexemestane

Better disease free survivalBetter disease free survival Women on exemestane had significantly more Women on exemestane had significantly more

visual disturbances, arthralgia, diarrhea, and visual disturbances, arthralgia, diarrhea, and osteoporosis, but women on tamoxifen had osteoporosis, but women on tamoxifen had significantly more gynecologic symptoms, significantly more gynecologic symptoms, muscle cramps, vaginal bleeding, muscle cramps, vaginal bleeding, thromboembolic disease, and second thromboembolic disease, and second malignancies other than breast cancer.malignancies other than breast cancer.

No difference was observed in overall survival No difference was observed in overall survival

Aromatase inhibitors: Aromatase inhibitors: letrozoleletrozole

Better disease free survivalBetter disease free survival Significantly more hot flashes, Significantly more hot flashes,

arthritis, arthralgia and myalgia, but arthritis, arthralgia and myalgia, but less vaginal bleeding. New diagnoses less vaginal bleeding. New diagnoses of osteoporosis were more frequent of osteoporosis were more frequent on letrozole on letrozole

Improvement in overall survivalImprovement in overall survival

Ovarian AblationOvarian Ablation

Surgery, radiation therapy or ovarian Surgery, radiation therapy or ovarian suppression with LHRH agonistssuppression with LHRH agonists

Ovarian suppression or ablation Ovarian suppression or ablation reduced the absolute risk of reduced the absolute risk of recurrence at 15 years by 4.3% and recurrence at 15 years by 4.3% and the risk of death from breast cancer the risk of death from breast cancer by 3.2.by 3.2.

ChemotherapyChemotherapy

CMF basedCMF based Anthracycline basedAnthracycline based

Duration of CMF-based Duration of CMF-based chemotherapychemotherapy

No survival benefit was No survival benefit was demonstrated for durations greater demonstrated for durations greater than 6 months.than 6 months.

Anthracycline basedAnthracycline basedchemotharapychemotharapy

Slight advantage for the anthracycline regimens in Slight advantage for the anthracycline regimens in both premenopausal and postmenopausal patients. both premenopausal and postmenopausal patients. Uncertainty remains, however, about whether there Uncertainty remains, however, about whether there is an advantage to combining both regimens.is an advantage to combining both regimens.

Evidence suggests that particular tumor Evidence suggests that particular tumor characteristics may predict anthracycline-characteristics may predict anthracycline-responsiveness. Data from retrospective analyses of responsiveness. Data from retrospective analyses of randomized clinical trials suggest that, in patients randomized clinical trials suggest that, in patients with node-positive breast cancer, the benefit is with node-positive breast cancer, the benefit is restricted to those patients whose tumors restricted to those patients whose tumors overexpress HER2/neu. The routine use of HER2/neu overexpress HER2/neu. The routine use of HER2/neu to select those patients that should or should not to select those patients that should or should not receive anthracycline-containing regimens should receive anthracycline-containing regimens should await further confirmation await further confirmation

Role of Preoperative Role of Preoperative adjuvant chemotherapyadjuvant chemotherapy

Preoperative chemotherapy may be Preoperative chemotherapy may be beneficial in women who desire beneficial in women who desire breast conservation surgery but who breast conservation surgery but who would otherwise not be considered would otherwise not be considered candidates because of the size of candidates because of the size of their tumor. their tumor.

Monoclonal antibodiesMonoclonal antibodies

Three clinical trials addressing the Three clinical trials addressing the role of the anti-HER2/neu antibody, role of the anti-HER2/neu antibody, trastuzumab, as adjuvant therapy for trastuzumab, as adjuvant therapy for patients with HER2 overexpressing patients with HER2 overexpressing cancers released the results of cancers released the results of interim analyses.interim analyses.

Highly significant improvement in Highly significant improvement in disease-free survival and overall disease-free survival and overall survivalsurvival

Risk Categories for Women Risk Categories for Women With Node-Negative Breast With Node-Negative Breast

Cancer Cancer Low risk Low risk (has all (has all listed listed factors) factors)    

IntermediIntermediate riskate risk

High risk High risk (has at (has at least 1 least 1 listed listed factor)factor)   

Tumor size Tumor size ≤≤1cm1cm 1-2 cm1-2 cm >2 cm>2 cm

ER or PR ER or PR Status Status

positive positive positive positive negativenegative

Tumor grade Tumor grade Grade 1Grade 1 grade 1-2grade 1-2 grade 2-3grade 2-3

Adjuvant systemic treatment Adjuvant systemic treatment for node negative for node negative

premenopausal womenpremenopausal womenPatient Patient groupgroup  

Low risk Low risk    IntermediIntermediate riskate risk  

High riskHigh risk   

ER-positive or ER-positive or PR-positive PR-positive

None or None or tamoxifen tamoxifen

1.T1.T±± C 2.Ov C 2.Ov Ab 3.GnRH Ab 3.GnRH analog analog

1.1. C & T C & T

2.2. C & Ov C & Ov Ab/ GnRH Ab/ GnRH analog analog

3.3. C & T & C & T & Ov Ab/ Ov Ab/ GnRH GnRH analoganalog

4.Ov ab 4.Ov ab ± T± T

5.GnRH 5.GnRH ±T±T

ER-negative ER-negative or PR-negativeor PR-negative

— — — — ChemotherapChemotherapy y

Adjuvant systemic treatment Adjuvant systemic treatment for node negative for node negative

postmenopausal womenpostmenopausal womenPatient Patient groupgroup  

Low risk Low risk    IntermediIntermediate riskate risk  

High riskHigh risk   

ER-positive or ER-positive or PR-positive PR-positive

None or None or tamoxifen tamoxifen

TT±± C C TT±± C C

ER-negative ER-negative or PR-negativeor PR-negative

— — — — ChemotherapChemotherapy y

Older than 70 Older than 70

yearsyears None or None or tamoxifen tamoxifen

TT±± C C T. Consider T. Consider chemotherapy chemotherapy if ER-negative if ER-negative

or PR-negativeor PR-negative

Adjuvant systemic treatment Adjuvant systemic treatment for node positive for node positive

premenopausal womenpremenopausal womenPatient group Patient group     TreatmentsTreatments   

ER or PR-positive ER or PR-positive 1.1. C & T C & T

2.2. C & Ov Ab/ GnRH analog C & Ov Ab/ GnRH analog

3.3. C & T & Ov Ab/ GnRH C & T & Ov Ab/ GnRH analoganalog

4. Ov ab 4. Ov ab ± T± T

5. GnRH 5. GnRH ±T±T

ER-negative or PR-negative ER-negative or PR-negative ChemotherapyChemotherapy

Adjuvant systemic treatment Adjuvant systemic treatment for node positive for node positive

postmenopausal womenpostmenopausal womenPatient group Patient group     TreatmentsTreatments   

ER or PR-positive ER or PR-positive T T ± C± C

ER-negative or PR-negative ER-negative or PR-negative ChemotherapyChemotherapy

Older than 70 yearsOlder than 70 years Tamoxifen alone; consider Tamoxifen alone; consider chemotherapy if receptor-chemotherapy if receptor-negative negative

Candidates for whom adjuvant Candidates for whom adjuvant therapy may not be necessarytherapy may not be necessary

Individuals with small primary tumors (<1 cm) Individuals with small primary tumors (<1 cm) and negative axillary nodes who have an and negative axillary nodes who have an excellent prognosis, with nearly 90% of patients excellent prognosis, with nearly 90% of patients alive and free of disease at 20 years in one alive and free of disease at 20 years in one series. series.

Proposals have been made to treat elderly Proposals have been made to treat elderly patients with tamoxifen alone and without patients with tamoxifen alone and without surgery. This approach has unacceptably high surgery. This approach has unacceptably high local failure rates and, outside of a clinical trial local failure rates and, outside of a clinical trial setting, should be used only for patients who are setting, should be used only for patients who are not candidates for mastectomy or breast-not candidates for mastectomy or breast-conserving surgery plus radiation therapy, or for conserving surgery plus radiation therapy, or for those who refuse these options.those who refuse these options.

Inoperable stage IIIB or IIIC or Inoperable stage IIIB or IIIC or inflammatory breast cancer inflammatory breast cancer

Multimodality therapy delivered with curative intent is the standard of Multimodality therapy delivered with curative intent is the standard of care for patients with clinical stage IIIB disease. care for patients with clinical stage IIIB disease.

32% of patients with ipsilateral supraclavicular node involvement and 32% of patients with ipsilateral supraclavicular node involvement and no evidence of distant metastases (pN3c) can have prolonged disease-no evidence of distant metastases (pN3c) can have prolonged disease-free survival at 10 years with combined modality therapy.This result free survival at 10 years with combined modality therapy.This result suggests such patients should be treated with the same intent. suggests such patients should be treated with the same intent.

Initial surgery is generally limited to biopsy to permit the Initial surgery is generally limited to biopsy to permit the determination of histology, ER and PR levels, and HER2/neu determination of histology, ER and PR levels, and HER2/neu overexpression. overexpression.

Initial treatment with anthracycline-based chemotherapy and/or Initial treatment with anthracycline-based chemotherapy and/or taxane-based therapy is standard. taxane-based therapy is standard.

For patients who respond to neoadjuvant chemotherapy, local therapy For patients who respond to neoadjuvant chemotherapy, local therapy may consist of total mastectomy with axillary lymph node dissection may consist of total mastectomy with axillary lymph node dissection followed by postoperative radiation therapy to the chest wall and followed by postoperative radiation therapy to the chest wall and regional lymphatics. Breast-conserving therapy can be considered in regional lymphatics. Breast-conserving therapy can be considered in patients with a good partial or complete response to neoadjuvant patients with a good partial or complete response to neoadjuvant chemotherapy. Subsequent systemic therapy may consist of further chemotherapy. Subsequent systemic therapy may consist of further chemotherapy. chemotherapy.

Hormone therapy should be administered to patients whose tumors Hormone therapy should be administered to patients whose tumors are ER-positive or unknown. are ER-positive or unknown.

Stage IV breast cancer Stage IV breast cancer

Treatment of metastatic breast cancer will Treatment of metastatic breast cancer will usually involve hormone therapy and/or usually involve hormone therapy and/or chemotherapy with or without chemotherapy with or without trastuzumab (Herceptin). Radiation trastuzumab (Herceptin). Radiation therapy and/or surgery may be indicated therapy and/or surgery may be indicated for patients with limited symptomatic for patients with limited symptomatic metastases. Fungating tumoursmetastases. Fungating tumours

Bisphosphonates to reduce skeletal Bisphosphonates to reduce skeletal morbidity in patients with bone morbidity in patients with bone metastases metastases

Stage IV breast cancer Stage IV breast cancer (cont)(cont)

Hormone therapy as initial treatment for a postmenopausal Hormone therapy as initial treatment for a postmenopausal patient with newly diagnosed metastatic disease if the patient with newly diagnosed metastatic disease if the patient’s tumor is ER-positive, PR-positive, or ER/PR-patient’s tumor is ER-positive, PR-positive, or ER/PR-unknown. Hormone therapy is especially indicated if the unknown. Hormone therapy is especially indicated if the patient’s disease involves only bone and soft tissue and the patient’s disease involves only bone and soft tissue and the patient has either not received adjuvant antiestrogen patient has either not received adjuvant antiestrogen therapy or has been off such therapy for more than 1 year. therapy or has been off such therapy for more than 1 year.

Women whose tumors are ER-positive or unknown, with Women whose tumors are ER-positive or unknown, with bone or soft tissue metastases only, who have received an bone or soft tissue metastases only, who have received an antiestrogen within the past year should be given second-antiestrogen within the past year should be given second-line hormone therapy. Examples of second-line hormone line hormone therapy. Examples of second-line hormone therapy in postmenopausal women include selective therapy in postmenopausal women include selective aromatase inhibitors, such as anastrozole, letrozole, or aromatase inhibitors, such as anastrozole, letrozole, or exemestane; megestrol acetate; estrogens; androgens; and exemestane; megestrol acetate; estrogens; androgens; and the ER down-regulator, fulvestrant.[ the ER down-regulator, fulvestrant.[

Stage IV breast cancer Stage IV breast cancer (cont)(cont)

Premenopausal women should undergo oophorectomy Premenopausal women should undergo oophorectomy (surgically, with external-beam radiation therapy or with an (surgically, with external-beam radiation therapy or with an LHRH agonist).LHRH agonist).

Patients with lymphangitic pulmonary metastases, major Patients with lymphangitic pulmonary metastases, major liver involvement, and/or central nervous system liver involvement, and/or central nervous system involvement should not receive hormone therapy as a single involvement should not receive hormone therapy as a single modality. Patients with structural compromise of weight-modality. Patients with structural compromise of weight-bearing bones should be considered for surgical intervention bearing bones should be considered for surgical intervention and/or radiation in addition to systemic therapy. Patients with and/or radiation in addition to systemic therapy. Patients with vertebral body involvement should be evaluated for vertebral body involvement should be evaluated for impending cord compression even in the absence of impending cord compression even in the absence of neurologic symptoms. Increasing bone pain and increasing neurologic symptoms. Increasing bone pain and increasing alkaline phosphatase within the first several weeks of alkaline phosphatase within the first several weeks of hormone therapy does not necessarily imply disease hormone therapy does not necessarily imply disease

Patients whose tumors have progressed on hormone therapy Patients whose tumors have progressed on hormone therapy are candidates for cytotoxic chemotherapy. Patients with are candidates for cytotoxic chemotherapy. Patients with hormone receptor-negative tumors and those with visceral hormone receptor-negative tumors and those with visceral metastases are also candidates for cytotoxic agents. metastases are also candidates for cytotoxic agents.

Follow-upFollow-up Evidence from randomized trials that periodic Evidence from randomized trials that periodic

follow-up with bone scans, liver sonography, chest follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not x-rays, and blood tests of liver function does not improve survival or quality of life when compared improve survival or quality of life when compared to routine physical examinations.Even when these to routine physical examinations.Even when these tests permit earlier detection of recurrent disease, tests permit earlier detection of recurrent disease, patient survival is unaffected.patient survival is unaffected.

Based on these data, some investigators Based on these data, some investigators recommend that acceptable follow-up be limited to recommend that acceptable follow-up be limited to physical examination and annual mammography physical examination and annual mammography for asymptomatic patients who complete for asymptomatic patients who complete treatment for stage I to stage III breast cancer. treatment for stage I to stage III breast cancer.