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1 Page 1 of 16 Breast Cancer – Invasive This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. CLINICAL STAGING INITIAL MULTIDISCIPLINARY EVALUATION 1 conservation therapy5 with sentinel6 lymph node (SLN) surgery 6 7 ● Total mastectomy with SLN surgery with or without reconstruction 8 ● Consider neoadjuvant chemotherapy for biologically aggressive tumors when appropriate. Confirm placement of radio-opaque markers.9 ● Breast 2,3 Pathology review ● Bilateral diagnostic mammography ● History and Physical ● CBC, platelets, liver function tests (total bilirubin, alkaline phosphatase, transaminases), creatinine ● Diagnostic imaging of breast and regional nodal basins with FNA of suspicious nodes ● In patients with clinical suspicion of distant metastasis body imaging4 recommended, consider for clinical stage IIb and III ● Consider need for genetic counseling, fertility preservation, and pregnancy testing ● Pre-operative lymphedema education and screening ● TREATMENT Clinical Stage I neoadjuvant chemotherapy8 or neoadjuvant endocrine therapy10 9 ● Confirm placement radio-opaque markers ● Consider Clinical Stage II/ Stage III Candidate for breast conservation5 at presentation? Yes No conservation therapy5 with axillary surgery11 ● Total mastectomy with axillary lymph node surgery with or without reconstruction7 or 8 ● Consider neoadjuvant chemotherapy (see page 2) See Page 2, Post Surgery See Page 3 ● Breast Yes Positive nodes? conservation therapy5 with SLN6 surgery 6 7 ● Total mastectomy with SLN surgery with or without reconstruction 8 ● Consider neoadjuvant chemotherapy ● Breast No See Page 2, PostSurgery There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 Pathology Review to include: ● Tumor size ● Composite histologic grade ● HER2 ● ER, PR receptor status ● Lymphatic/Vascular invasion ● Size of metastasis ● Lymph node status ● Histologic type ● Margin status ● Extracapsular extension ● Focal less than 2 mm or gross greater than 2 mm 3 Consider MD Anderson approved Breast biomarkers http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-tools-and-resources/practice-algorithms/clin-management-biomarkers-web-algorithm.pdf 4 Body imaging: CT abdomen, bone scan, chest x-ray preferred for initial imaging. CT chest optional. PET-CT for inflammatory breast cancer. 5 Candidates for breast conservation therapy: ● unicentric disease ● tumor to breast size ratio allows for acceptable cosmetic result ● Negative margins ● resolution of any skin edema after systemic therapy ● no evidence of diffuse calcifications on mammogram ● No contraindication to radiotherapy 6 Surgeons with an established record of lymphatic mapping experience for breast cancer (a minimum of 20 cases with an identification rate of greater than 85% and a false negative rate of less than 5%) may consider sentinel lymph node surgery as the initial and primary means of evaluating nodal status for selected patients who are clinically node negative. 7 For patients with stage II disease requiring post-mastectomy radiation, consider delayed reconstruction. For patients with stage III disease, delayed reconstruction is preferred. 8 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options 9 Radio-opaque markers should be placed as close to initiation of therapy as possible if not done at time of diagnosis. 10 See Page 11 for Endocrine Systemic Adjuvant Therapy Options 11 Candidates for limited axillary surgery with a prior biopsy proved axillary lymph node: documented removal of the prior biopsied and clipped lymph node demonstrating no metastases using sentinel lymph node Department of Clinical Effectiveness V14 dissection with targeted axillary dissection to ensure that lymph node with prior documented carcinoma is removed and tested. Copyright 2016 The University of Texas MD Anderson Cancer Center Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Breast Cancer – Invasive Page 2 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. ADJUVANT THERAPY FOLLOWING SURGERY AS LOCAL TREATMENT PATHOLOGICAL STAGING POSTSURGERY Yes Meets Z0011 criteria2? Yes ● ● No Positive Nodes? No further axillary surgery Tumor less than or equal to 0.5 cm Completion Axillary Lymph Node Dissection (ALND) ● Adjuvant chemotherapy3 with weekly anthracycline/taxane-based regimen5 Anti-HER2 based therapy3 regimen if HER2 positive Adjuvant endocrine therapy4 if tumor is hormone receptor positive Consider endocrine therapy4 if tumor is hormone receptor positive 5 ● Anti-HER2 based therapy if HER2 positive (consider weekly paclitaxel as chemotherapy backbone) ● Consider adjuvant chemotherapy3 for adverse prognostic features6 5 ● Use anti-HER2 based therapy for HER2 positive disease (consider weekly paclitaxel as chemotherapy backbone) 4 ● Adjuvant endocrine therapy if tumor is hormone receptor positive ● Consider multi-gene prognostic assays, see Appendix B ● No Tumor greater than 0.5 to 1 cm ● Tumor greater 1 cm7 ● ● ● See Page 4 For Radiotherapy Options Consider adjuvant chemotherapy3 when appropriate5 Anti-HER2 based therapy if HER2 positive5 Adjuvant endocrine therapy4 if tumor is hormone receptor positive Consider multi-gene prognostic assays, see Appendix B 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 Z0011 criteria: Clinical T1 or T2, N0, M0, lumpectomy and sentinel lymph node surgery, and tumor positive sentinel node (up to two nodes positive on sentinel node surgery) planned for whole breast irradiation and systemic therapy. 3 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options 4 See Page 11 for Endocrine Systemic Adjuvant Therapy Options 5 Cardiac evaluation at baseline and as clinically indicated 6 Lymphovascular invasion (LVI), triple receptor negative, High-grade 3. 7 Tumors of favorable histology less than 3.0 cm (tubular, mucinous) can be considered lower risk and treated appropriately. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Breast Cancer – Invasive Page 3 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. LOCAL TREATMENT CLINICAL STAGE/ PRESENTATION Assess tumor size at least every 6 weeks and at completion of systemic treatment with physical exam ● Imaging with mammogram and/or ultrasound at completion of systemic treatment, if undergoing breast conserving surgery ● Consider midtreatment ultrasound or other imaging at any point for clinical suspicion of disease progression ● Neoadjuvant systemic chemotherapy3 OR neoadjuvant endocrine therapy4 as clinically indicated ● If candidate for breast conservation therapy5 following neoadjuvant therapy, place radioopaque markers Yes Anti-HER2 based therapy options3,6 HER2 positive? No Chemotherapy (or hormone therapy options if appropriate) for HER2-negative breast cancer3,4,6 Yes Breast conservation therapy candidate5? No 1 Breast Conserving Surgery5 ● If clinically node negative at diagnosis, proceed with sentinel node surgery7 followed by axillary node surgery if sentinel node is positive ● If clinically node positive, confirmed by needle biopsy proceed with axillary node dissection or if limited axillary nodal disease is no longer evident, consider SLN biopsy with documented clip removal and if no metastases proceed to radiotherapy without axillary lymph node dissection Total mastectomy with nodal treatment as determined by initial nodal status: ● If clinically node negative at diagnosis, proceed with sentinel node biopsy7 followed by axillary node surgery if sentinel node positive ● If clinically node positive, confirmed by needle biopsy proceed with axillary node dissection or if limited axillary nodal disease is no longer evident, consider SLN biopsy with documented clip removal and if no metastases proceed to radiotherapy without axillary lymph node dissection ● Consider reconstruction and plastic surgery consult8 See Pathological Findings on Page 4 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 3 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options 4 See Page 11 for Endocrine Systemic Adjuvant Therapy Options. Higher risk patients could be considered for post-operative chemotherapy. 5 Candidates for breast conservation therapy: ● unicentric disease ● tumor to breast size ratio allows for acceptable cosmetic result ● margins greater than or equal to 2 mm, ● resolution of any skin edema after systemic therapy ● no evidence of diffuse calcification on mammogram ● No contraindication to radiotherapy 6 Cardiac evaluation at baseline and as clinically indicated 7 Surgeons with an established record of lymphatic mapping experience for breast cancer (a minimum of 20 cases with an identification rate of greater than 85% and a false negative rate of less than 5%) may consider sentinel lymph node dissection as the initial and primary means of evaluating nodal status for selected patients who are clinically node negative. 8 For patients with stage II disease requiring post-mastectomy radiation, consider delayed reconstruction. For patients with stage III disease, delayed reconstruction is preferred. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Breast Cancer – Invasive Page 4 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. PATHOLOGICAL FINDINGS TREATMENT ● Stage I - II disease, with 0-3 involved lymph node(s) ● ● From local treatment Stage III disease or 4 or more involved lymph nodes ● ● Whole breast radiotherapy2 for breast conservation therapy with or without regional lymphatics. Consider partial breast radiotherapy for tumors less than or equal to 3 cm and negative lymph nodes. XRT consult for consideration of chest wall radiotherapy with or without regional lymphatics for patients with total mastectomy and tumor greater than 5 cm or any positive lymph nodes. Post mastectomy radiotherapy to chest wall and regional lymphatics Whole breast radiotherapy2 with regional lymphatics for breast conservation therapy SURVEILLANCE Physical exam at least every 6 months 10 after year 5 for 5 years, then annually ● If breast conservation therapy, mammogram of treated breast at 6-12 months, then annually ● Annual gynecologic exam, if receiving tamoxifen ● Assess bone health (See Breast Cancer Survivorship: Bone Health Algorithm) ● Encourage age appropriate cancer and general health guidelines ● Educate, screen and refer for lymphedema management as needed ● Endocrine therapy3 for hormone receptor positive tumors sequential after chemotherapy4 and local therapy ● Trastuzumab to complete one year if HER2-positive tumor ● 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 Radiotherapy for BCT and post-mastectomy radiation, are generally delivered at completion of chemotherapy. For early stage node negative patients, radiotherapy may be delivered before or after chemotherapy. 3 See Page 11 for Endocrine Systemic Adjuvant Therapy Options 4 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Page 5 of 16 Breast Cancer – Invasive This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. EVALUATION FOR METASTASIS TREATMENT FOR METASTASIS Premenopausal endocrine options3 Distant metastasis1,2 ER positive and bone or soft tissue metastasis only or ● Limited visceral disease ● ● Biopsy to confirm metastatic disease, histology, ER/PR and HER2 status ● Bone Scan ● CT, PET/CT or MRI to encompass chest, abdomen and pelvis ● Consider chest x-ray if no CT is performed ● Complete blood count and chemistries including renal and liver function ● Consider CA15-3 as an adjunctive test for monitoring response to therapy HER2 negative ER negative or ● ER positive and extensive visceral disease or ● Symptomatic disease ● ● ● Tamoxifen with or without ovarian ablation In premenopausal patient following ovarian ablation use post-menopausal endocrine options Yes Non-steroidal aromatase inhibitors with or without fulvestrant (if no prior aromatase inhibitor or tamoxifen) ● Tamoxifen (if no prior tamoxifen) ● Letrozole with or without Palbociclib Second line therapy: ● Exemestane with or without everolimus ● Fulvestrant with or without Palbociclib ● Other endocrine treatments: ● Estrogens ● Progestins ● Androgens ● Postmenopausal endocrine options3 Chemotherapy5 until progressive disease or maximum benefit can include: ● Anthracyclines based ● Carboplatin ● Ixabepilone upon lifetime exposure ● Cisplatin ● Taxanes to anthracyclines ● Eribulin ● Vinorelbine ● Capecitabine ● Gemcitabine HER2 positive by either Immuno-histochemistry 3+ or FISH 1 Disease response or clinical benefit?4 Continue current treatment until progressive disease or unacceptable toxicity then consider alternate endocrine therapy3 No Failure to respond to 3 sequential regimens or Zubrod status greater than or equal to 3, discontinue chemotherapy Palliative care See Page 6 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 See Appendix B for scenarios requiring individualized therapy. 3 See Page 11 for Endocrine Systemic Adjuvant Therapy Options. Male patients should be treated similarly to premenopausal patients. Use of aromatase inhibitors or fulvestrant should be accompanied by androgen deprivation therapy (medical/surgical). Copyright 2016 The University of Texas MD Anderson Cancer Center NOTE: All patients with bone metastases and life expectancy greater than 12 weeks should consider after dental evaluation: a bisphosphonate (creatinine clearance is 30 or greater) or denosumab. 4 Consider breast surgery for patients with limited responding metastatic disease who have an intact primary. 5 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options ER = Estrogen Receptor FISH = Fluorescence In Situ Hybridization HER2 = Human Epidermal Growth Factor Receptor 2 PR = Progesterone Receptor Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Page 6 of 16 Breast Cancer – Invasive This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. TREATMENT FOR METASTASIS NOTE: All patients with bone metastases and life expectancy greater than 12 weeks should consider after dental evaluation: a bisphosphonate (creatinine clearance is 30 or greater) or denosumab. Continued from previous page HER2 positive by either Immunohistochemistry 3+ or FISH If no prior trastuzumab or greater than 1 year since adjuvant trastuzumab: ● Taxane chemotherapy plus trastuzumab plus pertuzumab ● Alternate therapy based on hormone receptor status if not candidate for anti-HER2 or cytotoxic therapy If less than 6 to 12 months from adjuvant trastuzumab or if prior (neo)adjuvant pertuzumab: ● T-DM-1(Ado-trastuzumab emtansine) 2 ● Consider HER2 directed therapies Progressive disease Proceed to one of the following regimens, and can follow by another regimen below if the patient continues to be a candidate for antineoplastic therapy: ● T-DM1 if not previously given ● Capecitabine plus lapatinib ● Trastuzumab plus lapatanib ● Trastuzumab plus other chemotherapy (preferred options - Vinorelbine, gemcitabine, capecitabine, eribulin) 3 ● Chemotherapy or hormonal therapy (if ER or PR positive) 2 ● Consider HER2 directed therapies Palliative care 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 3 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options 2 See Appendix C - Recurrent or Metastatic Breast Cancer Treatment Options ER = Estrogen Receptor FISH = Fluorescence In Situ Hybridization HER2 = Human Epidermal Growth Factor Receptor 2 PR = Progesterone Receptor Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Page 7 of 16 Breast Cancer – Invasive This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. TREATMENT FOR RECURRENCE EVALUATION FOR LOCAL RECURRENCE Ipsilateral breast/chest wall recurrence or ipsilateral regional recurrence without distant metastasis Total mastectomy with lymph node surgery consider sentinel lymph node surgery if clinically node negative 3,4 ● Consider systemic therapy 3 ● Consider pre-operative chemotherapy Yes Previous breast radiotherapy? Yes Invasive histology? No (e.g. DCIS) Breast conservation therapy with margin assessment, or ● Total mastectomy; lymph node surgery; radiation therapy consult ● Biopsy to confirm recurrence with: ● Consider body imaging for invasive recurrence ● If intact breast, bilateral diagnostic mammogram ● Ultrasound of affected breast including regional nodal basins ● Consider preoperative systemic therapy 2 ● Consider biomarkers No Yes Breast intact? No Yes No Yes Consider systemic therapy No Radiotherapy to chest wall, and regional lymphatics (if not DCIS alone) Previous chest wall radiotherapy? Surgical resection with margin assessment Yes Resectable? No Surveillance and endocrine therapy if estrogen receptor positive Yes Resectable? Endocrine therapy4 or HER2-directed therapy with or without chemotherapy3 1 Wide local excision (WLE) with margin assessment ● Consider neoadjuvant systemic therapy prior to WLE ● Consider systemic therapy ● Consider pre-operative chemotherapy3 ● ● Radiotherapy to chest wall and regional lymphatics, if no previous radiation Persistent disease? Consider additional systemic therapy Surveillance and endocrine therapy if hormone receptor positive ● Consider chemotherapy ● No There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 Consider MD Anderson approved Breast biomarkers http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-tools-and-resources/practice-algorithms/clin-management-biomarkers-web-algorithm.pdf 3 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options 4 See Page 11 for Endocrine Systemic Adjuvant Therapy Options Department of Clinical Effectiveness V14 Copyright 2016 The University of Texas MD Anderson Cancer Center Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Breast Cancer – Invasive Inflammatory Breast Cancer Page 8 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. TREATMENT STAGING Modified radical mastectomy ● Radiotherapy to chest wall and regional lymphatics, if no previous radiation3 4 ● Adjuvant endocrine therapy if tumor is hormone receptor positive5 HER2 positive ● HER2 negative: neoadjuant doxorubicin and taxane based chemotherapy2 ● HER2 positive: dual anti-HER2 therapy containing regimen with chemotherapy ● Consider clinical trial(s) ● Stage III2 Stage IV2 (de novo) Multidisciplinary evaluation of response Yes Operable? HER2+ maintenance therapy ● HER2 ● Hormone receptors Hormone receptor positive Adjuvant endocrine therapy Yes No Additional systemic therapy5 with or without radiotherapy Additional systemic therapy ● Symptom management (supportive care) ● Consider clinical trial(s) ● Multidiciplinary evaluation of response Operable? No Single/multi-agent systemic therapy ● Symptom management (Supportive care) ● Clinical trials ● 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Patients with limited life expectancy ● Cancer during pregnancy 2 Diagnostic Workup: ● Medical history and physical ● Obtain photograph to establish baseline clinical appearance and follow up medical photography for a treatment response documentation. ● PET scan/CT scan- If PET/CT scan not possible: neck (if clinically indicated) in addition to chest/abdominal pelvic CT with bone scan. ● Obtain skin biopsy and ultrasound guided core biopsy of the tumor (random biopsies if mass not present) 3 Evaluate pathology response: ● Minimal residual disease or pathologic complete response, age over 45 and negative margins, daily radiation to 66 Gy (2 Gy/fraction, primary fields to 50). ● Significant residual disease, age less than 45 or close or positive margins, twice daily radiation to 66 Gy (1.5 Gy per fraction, primary fields to 51). 4 See Page 11 for Endocrine Systemic Adjuvant Therapy Options 5 See Appendix A - Neoadjuvant/Adjuvant Chemotherapy Options ● Sarcoma of the breast ● Lymphoma of the breast Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 1 Page 9 of 16 Breast Cancer – Invasive This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. APPENDIX A: Neoadjuvant/Adjuvant Chemotherapy Options2 HER-2 negative disease3 Preferred regimens: ● Doxorubicin and cyclophospamide (AC) either every 3 weeks or every 2 weeks (dose dense) followed or preceded by weekly paclitaxel x 12, or dose dense paclitaxel every 2 weeks ● Fluorouracil, doxorubicin, and cyclophosphamide (FAC) followed or preceded by weekly paclitaxel Other regimens4: ● Dose-dense doxorubicin and cyclophospamide (AC) followed or preceded by paclitaxel every 2 weeks ● Docetaxel and cyclophosphamide (TC) ● Dose-dense doxorubicin and cyclophospamide (AC) followed or preceded by docetaxel every 3 weeks HER-2 positive disease Preferred regimens: ● Doxorubicin and cyclophospamide (AC) followed by paclitaxel plus trastuzumab and pertuzumab cycles/ days vary ● Docetaxel, carboplatin, trastuzumab (TCH) plus pertuzumab ● For Stage II or higher, consider addition of pertuzumab with chemotherapy portion of regimen. Other regimens4: ● Weekly paclitaxel plus trastuzumab (for low-risk disease, such as Stage I) APPENDIX B: Clinical Scenarios Requiring Individualized Therapy Brain metastases Ureteral obstruction ● Leptomeningeal disease ● Impending pathologic fracture ● Choroid metastases ● Pathologic fracture ● Extensive local-regional disease ● Pleural effusion Cord compression Pericardial effusion ● Plexopathy/radiculopathy ● Biliary obstruction ● Superior vena cava syndrome ● Stage IV NED ● Oligometastasis5 ● Pregnancy ● ● ● ● Copyright 2016 The University of Texas MD Anderson Cancer Center 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: Sarcoma of the breast ● Patients with lupus and scleroderma Special histologies (i.e., tubular, medullary, pure papillary, or colloid) Lymphoma of the breast ● Patients with limited life expectancy Cancer during pregnancy 2 Refer to NCCN Guidelines Version 3.2015. for specific doses and number of cycles. 3 Optimal duration of adjuvant HER-2 therapy is one year. 4 May consider other neoadjuvant/adjuvant regimens per NCCN guidelines 5 Oligometastases – selected patients with isolated metastatic breast cancer may be considered for definitive treatment. ● ● ● ● Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive1 Page 10 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients or other regimens as suggested by NCCN guidelines. APPENDIX C: Recurrent or Metastatic Breast Cancer Treatment Options Preferred Single Agents: Anthracyclines ● Doxorubicin ● Pegylated liposomal doxorubicin Other Single Agents: ● Cyclophosphamide ● Carboplatin Taxanes ● Paclitaxel ● ● Anti-metabolites ● Capecitabine ● Gemcitabine Docetaxel Albumin-bound paclitaxel ● ● Other microtubule inhibitors ● Vinorelbine ● Eribulin Cisplatin Epirubicin ● Ixabepilone Combination Chemotherapy Regimens: ● ● ● ● ● FAC/CAF (cyclophosphamide, doxorubicin, and fluorouracil) FEC (fluorouracil, epirubicin, and cyclophosphamide) AC (doxorubicin and cyclophosphamide EC (epirubicin and cyclophosphamide) CMF (cyclophosphamide, methotrexate, and fluorouracil) ● ● ● ● Docetaxel and capecitabine Gemcitabine and paclitaxel) Gemcitabine and carboplatin Ixabepilone/capecitabine First-line Regimens for HER2-positive disease2: (trastuzumab naïve patients or those who recurred after 6 to 12 months after adjuvant trastuzumab) ● Pertuzumab plus trastuzumab and docetaxel ● Pertuzumab plus trastuzumab and paclitaxel Other Options, but should not be considered preferred first options: ● Trastuzumab with docetaxel ● Trastuzumab with paclitaxel with or without carboplatin ● ● Trastuzumab with vinorelbine Trastuzumab with capecitabine Regimens for trastuzumab-exposed HER2-positive disease2: ● Ado-trastuzumab emtansine (T-DM1) for recurrence (6 to 12 months from adjuvant trastuzumab) ● Lapatinib plus capecitabine ● Trastuzumab plus lapatinib without cytotoxic therapy ● Trastuzumab plus capecitabine ● Trastuzumab plus other agents Copyright 2016 The University of Texas MD Anderson Cancer Center 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 After maximal benefit achieved with chemotherapy, consider continuous anti-HER2 therapy alone, if ER or PR positive in combination with appropriate hormonal therapy (This does not apply to Ado-trastuzumab emtansine [T-DM1]) Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive1 Page 11 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. NOTE: Consider clinical trials as treatment options for eligible patients. Endocrine Systemic Adjuvant Therapy Options Yes Tamoxifen for 5 years with or without ovarian suppression or ablation Postmenopausal after initial 5 years? Premenopausal at diagnosis2 No ● ● ● ● Aromatase inhibitor for 5 years or Consider tamoxifen for an additional 5 years (10 years total) Consider tamoxifen for an additional 5 years (10 years total) No further endocrine therapy Ovarian ablation plus aromatase inhibitor for at least 5 years ● ● Yes ● ● ● Postmenopausal at diagnosis Aromatase inhibitor an option3? ● No ● ● Aromatase inhibitor for at least 5 years or Tamoxifen for 2-3 years followed by aromatase inhibitor to complete at least 5 years of endocrine therapy or Tamoxifen for 2-3 years followed by aromatase inhibitor for at least 5 years or Aromatase inhibitor for 2-3 years followed by tamoxifen to complete at least 5 years of endocrine therapy Tamoxifen for 4 ½ to 6 years followed by aromatase inhibitor to for at least 5 years or Tamoxifen for 4 ½ to 6 years, then consider tamoxifen for an additional at least 5 years for a total of 10 years of endocrine therapy Tamoxifen for 5 years or Consider tamoxifen for up to 10 years 1 There are special circumstances in which these guidelines do not apply. These include, but are not limited to: ● Sarcoma of the breast ● Patients with lupus and scleroderma ● Special histologies (i.e., tubular, medullary, pure papillary, or colloid) ● Lymphoma of the breast ● Patients with limited life expectancy ● Cancer during pregnancy 2 Male patients should be treated similarly to premenopausal patients. Use of aromatase inhibitors or fulvestrant should be accompanied by androgen deprivation therapy (medical/surgical). 3 Aromatase inhibitors may not be an option if the patient is intolerant, concerns over bone density or patient declines therapy. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive Page 12 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. SUGGESTED READINGS Albain KS, Barlow WE, Ravdin PM, et al. (2009). Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet; 374(9707):2055-63. Baselga J, Campone M, Piccart M, et al. (2012). Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med; 366(6): 520-9. Baselga J, Cortes J, Kim SB, et al. (2012). CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med; 366(2):109-19. Bear H, Anderson S, Smith R, et al. (2006). Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol; 24(13):2019-27. Breast. In: Edge SB, Byrd SR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:347-376. Buchholz TA, Theriault RL, Niland JC, et al. (2006). The use of radiation as a component of breast conservation therapy in National Comprehensive Cancer Network Centers. J Clin Oncol; 24(3):361-9. Buchholz TA. (2009). Radiation therapy for early-stage breast cancer after breast-conserving surgery. N Engl J Med; 360(1):63-70. Burstein HJ, Prestrud AA, Seidenfeld J, et al. (2010). American Society of Clinical Oncology clinical practice guideline: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol; 28(23):3784-3796. Buzdar A, Ibrahim N, Francis D, et al. (2005). Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol; 23(16):3676-85. Caudle AS, Gonzalez-Angulo AM, Hunt KK, et al. (2010). Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. J Clin Oncol; 28(11):1821-8. Caudle AS, Hunt KK, Kuerer HM, et al. (2011). Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practicechanging trial. Ann Surg Oncol; 18(9):2407-12. Caudle AS & Kuerer HM. (2015). Targeting and limiting surgery for patients with node-positive breast cancer. BMC Med, 13:149. doi: 10.1186/s12916-015-0385-5. Caudle AS, Yang WT, Mittendorf EA, Black DM, Hwang R, Hobbs B, Hunt KK, Krishnamurthy S, & Kuerer HM. (2015). Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surg, 150(2):137-43. Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, Bedrosian Isabelle…& Kuerer H. (2016). Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol (in press) Clarke M, Collins R, Darby S, et al. (2005). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Lancet; 366(9503):2087-106. Early Breast Cancer Trialists' Collaborative Group. (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet; 365(9472):1687-1717. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale P, Taylor C, Correa C, et al. (2014). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet; 383(9935):2127-35. Fearmonti RM, Vicini FA, Pawlik TM, et al. (2007). Integrating partial breast irradiation into surgical practice and clinical trials. Surg Clin North Am; 87(2):485-98. Fisher B, Bryant J, Wolmark N, et al. (1998). Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol; 16(8):2672-85. Fisher B, Jeong JH, Anderson S, et al. (2002). Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med; 347(8):567-75. Floyd SR, Buchholz TA, Haffty BG, et al. (2006). Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger. Int J Radiat Oncol Biol Phys; 66(2):358-64. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive Page 13 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. SUGGESTED READINGS - Continued Foulkes WD, Smith IE, Reis-Filho JS. (2010). Triple-negative breast cancer. N Engl J Med; 363(20):1938-48. Gennari A, Stockler M, Puntoni M, et al. (2011). Duration of chemotherapy for metastatic breast cancer: a systematic review and meta-analysis of randomized clinical trials. J Clin Oncol; 29(16):2144-9. Gianni L, Eiermann W, Semiglazov V, et al. (2010). Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2positive locally advanced breast cancer (the NOAH trial): A randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet; 375(9712):377-84. Gianni L, Pienkowski T, Im YH, et al. (2012). Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol; 13(1):25-32. Giordano SH, Kuo YF, Freeman JL, et al. (2005). Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst; 97(6):419-24. Giuliano AE, Hunt KK, Ballman KV, et al. (2011). Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA; 305(6):569-75. Giuliano AE, McCall L, Beitsch P, et al. (2010). Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg; 252(3):426–33. Huang EH, Strom EA, Valero V, et al. (2007). Locoregional treatment outcomes for breast cancer patients with ipsilateral supraclavicular metastases at diagnosis. Int J Radiat Oncol Biol Phys;67(2):490-6. Hunt KK, Yi M, Mittendorf EA, et al. (2009). Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. Ann Surg; 250(4):558-66. Jeruss J, Mittendorf E, Tucker S, et al. (2008).Combined use of clinical and pathologic staging variables to define outcomes for breast cancer patients treated with neoadjuvant therapy. J Clin Oncol; 26(2):246-52. Jones SE, Savin MA, Holmes FA, et al. (2006). Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol; 24(34):5381-5387. Kelly CM, Hortobagyi GN. (2010). Adjuvant chemotherapy in early-stage breast cancer: what, when, and for whom? Surg Oncol Clin N Am; 19(3):649-68. Krag DN, Anderson SJ, Julian TB, et al. (2010). Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol; 11(10):927-33. Krag DN, Anderson SJ, Julian TB, et al. (2007). Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol; 8(10):881-8. Kuerer H, Sahin A, Hunt K, et al. (1999). Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg; 230(1):72-8. Kuerer HM, Hunt KK, Newman L, et al. (2000). Neoadjuvant chemotherapy in women with invasive breast carcinoma: conceptual basis and fundamental surgical issues. J Am Coll Surg; 190(3):350-63. Kuerer HM, Newman LA, Smith TL, et al. (1999). Clinical course of breast cancer with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol; 17(2):460-9. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive Page 14 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. SUGGESTED READINGS - Continued Lucci A, McCall LM, Beitsch PD, et al. (2007). American College of Surgeons Oncology Group. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group trial Z0011. J Clin Oncol; 25(24):3657–63. Mehta RS, Barlow WE, Albain KS, et al. (2012). Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med; 367(5):435-44. Mittendorf EA, Buchholz TA, Tucker SL, et al. (2013). Impact of chemotherapy sequencing on local-regional failure risk in breast cancer patients undergoing breast-conserving therapy. Ann Surg; 257(2):173-9. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Version 3.2015. Paik S, Shak S, Tang G, et al. (2004). A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Eng J Med; 351:2817-26. Paik S, Tang G, Shak S, et al. (2006). Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol; 24(23):3726-34. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. (2005). Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med; 353(16):1659-1672. Pritchard KI, Shepherd LE, O’Malley FP, et al. (2006). HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med; 354(20):2103-11. Prudence A, Francis MD, Meredith, MR, et al (2015). Adjuvant ovarian suppression in premenopausal breast cancer. N England J Med; 372:436-446. PMID: 25495490 doi: 10.1056/NEJMoa1412379. Epub 2014 Dec 11. Romond EH, Perez EA, Bryant J, et al. (2005). Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med; 353(16):1673-1684. Schneeweiss A, Chia S, Hickish T, et al. (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol; 24(9):2278-84. Smith BD, Arthur DW, Buchholz TA, et al. (2009). Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). J Am Coll Surg; 209(2):269-77. Smith BD, Haffty BG, Buchholz TA, et al. (2006). Effectiveness of radiation therapy in older women with ductal carcinoma in situ. J Natl Cancer Inst; 98(18):1302-10. Smith BD, Haffty BG, Smith GL, et al. (2008). Use of postmastectomy radiotherapy in older women. Int J Radiat Oncol Biol Phys; 71(1):98-106. Sparano JA, Wang M, Martino S, et al. (2008). Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med; 358(16):1663-71. Symmans W, Peintinger F, Hatzis C, et al. (2007). Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol; 25(28):4414-22. Tolaney SM, Barry WT, Dang CT, et al. (2015). Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med; 372(2):134-41. Veronesi U, Viale G, Paganelli G, et al. (2010). Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg; 251(4):595–600. Vicini F, Beitsch P, Quiet C, et al. (2011). Five-year analysis of treatment efficacy and cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys; 79(3):808-17. Yamauchi H, Woodward WA, Valero V, et al. (2012). Inflammatory breast cancer: What we know and what we need to learn. Oncologist; 17(7):891-9. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive Page 15 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. SUGGESTED READINGS – Chemotherapy Regimens for Metastatic Breast Cancer and in Combination with Transtuzumab Burstein HJ, Kuter I, Campos SM, et al. (2001). Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol,19,2722-30. Cobleigh MA, Vogel CL, Tripathy D, et al. (1999). Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2- Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease. J Clin Oncol, 17,2639-48. Esteva FJ, Valero V, Booser D, et al. (2002). Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER2-Overexpressing Metastatic Breast Cancer. J Clin Oncol, 20,1800-1808. Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. NEJM,355,2733-43. Gradishar WJ, Tjulandin S, Davidson N, et al. (2005). Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil-Based Paclitaxel in Women With Breast Cancer. J Clin Oncol 23:7794-7803 Leyland-Jones, Gelmon, Ayoub JB, et al. (2003). Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination with Paclitaxel. J Clin Oncol 21, 3965-3971. O’Brien, M. E., Wigler, N., Inbar M, et al. (2004). Reduced Cardiotoxicity and Comparable Efficacy in a Phase lll Trial of Pegylated Liposomal Doxorubicin HC1 (CAELYX/Doxil) vs. Conventional Doxorubicin for First-Line Treatment of Metastatic Breast Cancer. Ann Oncol, 15(3), 440-9. Perez E. (2004). Carboplatin in combination therapy for metastatic breast cancer. The Oncologist, 9,518-527. Slamon DJ, Leyland-Jones B, Shak S, et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 344,783-92. Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016 Breast Cancer – Invasive Page 16 of 16 This practice algorithm has been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population; MD Anderson’s services and structure; and MD Anderson’s clinical information. Moreover, this algorithm is not intended to replace the independent medical or professional judgment of physicians or other health care providers. This algorithm should not be used to treat pregnant women. DEVELOPMENT CREDITS This practice consensus algorithm is based on majority expert opinion of the Breast Center Faculty at the University of Texas MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following breast multidisciplinary team members. Sausan Abouharb, MD Beatriz Adrada, MD Catherine Akay, MD Constance Albarracin,MD Frederick Ames, MD Elsa Arribas, MD Banu K. Arun, MD Carlos Barcenas, MD Robert C. Bast, MD Gildy Babiera, MD Isabelle Bedrosian, MD Daniel J. Booser, MD Shon Black, MD Abenna Brewster, MD Powel Brown, MD Thomas Buchholz, MD Aman U. Buzdar, MD Abigail Caudle, MD Mariana Chavez-Mac Gregor, MD Hui Chen, MD Alejandro Contreras, MD Sarah DeSnyder, MD Mark Dryden, MD Mary Edgerton, MD Barry Feig, MD Bruno Fornage, MD Michael Gilcrease, MD Sharon Giordano, MD Tamara Haygood, MD Karen Hoffman, MD Gabriel N. Hortobagyi, MD Kelly K. Hunt, MD Ŧ Lei Huo, MD Rosa Hwang, MD Nuhad K. Ibrahim, MD Meghan Karuturi, MD Kimberly Koenig, MD Savitri Krishnamurthy, MD Henry M. Kuerer, MD, PhD Deanna Lane, MD Huong Le-Petross, MD Jennifer Litton, MD Ŧ Anthony Lucci, MD Funda Meric-Bermstam, MD Lavinia Middleton, MD Elizabeth Mittendorf, MD, PhD Stacy Moulder, MD James L. Murray,III, MD Rashmi Murthy, MD George Perkins, MD Erika Resetkova, MD Merrick I. Ross, MD Aysegul A. Sahin, MD Lumarie Santiago, MD Simona Shaitelman, MD Benjamin Smith, MD Nour Sneige, MD Tanya Moseley, MD Michael Stauder, MD Eric Strom, MD Fraser W. Symmans, MD Welela Tereffe, MD Ŧ Mediget Teshome, MD Alastair Thompson, MD Debasish Tripathy, MD Naoto T. Ueno, MD, PhD Vicente Valero, MD Ronald Walters, MD Gary Whitman, MD Wendy Woodward, MD Yun Wu, MD Wei Yang, MD Amy Zhang, MD ŦCore Development Team Copyright 2016 The University of Texas MD Anderson Cancer Center Department of Clinical Effectiveness V14 Approved by Executive Committee of the Medical Staff on 06/28/2016