Breast Cancer (2011) Philippine Society of Oncology, Inc.

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1 (2011) Philippine Society of Oncology, Inc. Rm. 803, orth Tower, Cathedral Heights Building Complex St. Luke s Medical Center, E. Rodriguez Sr. Ave. Quezon City, 1102 Philippines Trunkline: local 5803 Telefax: philsoco_pso@yahoo.com Website:

2 Philippine Society of Oncology, Inc. Rm. 803, orth Tower, Cathedral Heights Building Complex St. Luke s Medical Center, E. Rodriguez Sr. Ave. Quezon City, 1102 Philippines Trunkline: local 5803 Telefax: philsoco_pso@yahoo.com Website: Officers 2011 President Vice-President Secretary Treasurer Immediate Past President Members, Executive Councils Jose S. Garcia, MD Romulo S. de Villa, MD Roel S. Tolentino, MD Charity Charise Viado Gorosbe, MD Enrico D. Tangco, MD Gonzalo C. Banwelos Jr., MD Luis P. Cruz, MD Jorge G. Ignacio, MD Cecilia L. Llave, MD Ramon S. Severino, MD l Sign up and open your clinic to the world. 37

3 Algorithm for the Management of Invasive Breast Cancer 1 Patient w/ Breast Cancer 2 History and PE of Patient 3 4 Palpable mass? Do Biopsy of the tumor (incisional, excisional, coreneedle) Mammography (For >35 y/o) and/or Breast Ultrasound Suspicious mass? - Mammographic needle localization biopsy - Ultrasound guided needle localization biopsy Follow-up as needed With cancer? - Request for ER, PR, HER2 - Metastatic work-up Follow-up as needed With metastasis? Chemotherapy as required 14 Offer breast conserving surgery if <4 cm See Figure 2 Legend: ER - Estrogen receptor PR - Progesterone receptor Figure 1 38

4 Figure For Breast Conserving Surgery? - Do lumpectomy if not done and axillary dissection - Radiation therapy 3 Modified radical mastectomy >1 cm tumor or >0.5 cm w/ poor prognostic signs? Chemotherapy Is lymph node (+)? Radiation therapy 8 9 Is lymph node (+)? Consider hormonal treatment if hormone receptor-positive or chemotherapy or radiation therapy ER (+) or PR(+)? Hormonal Treatment Follow-up as needed Follow-up as needed Follow-up as needed * HER2 (+) patient are treated by trastuzumab Figure 2 Learn to access drug info on your cellphone. Send PPD to 2600 for Globe/Smart/Sun users. 39

5 Breast Cancer Invasive Ductal Carcinoma Consensus Guidelines by the Philippine Society of Oncology (2009) In women who need to be worked-up for breast cancer, several steps must be followed to ensure proper diagnosis and treatment. Recommended procedures to be done in patients suspected of having breast cancer History and physical examination. Complete blood count. Liver function tests and alkaline phosphatase. Ultrasonography of the breasts or diagnostic bilateral mammogram for patients more than 35 years old. Core needle biopsy, incision biopsy, or excision biopsy of the breast tumor. Determination of tumor estrogen/ progesterone receptor (ER/PR) status and HER2 status are requested if malignancy is found. 40 AJCC TM STAGIG, 6 th Edition 1 TUMOR SIZE [T] TX: the primary breast cancer cannot be (or has not yet been) found or sized/measured T0: no evidence of primary tumor Tis: carcinoma in situ Tis (DCIS): Ductal carcinoma in situ Tis (LCIS): Lobular carcinoma in situ Tisc (Paget s): Paget s disease of the skin/nipple with no tumor T1: the tumor is 2 cm. (centimeters) or less in greatest dimension T1mic: microinvasive, 0.1 cm. or less in greatest dimension T1a: tumor greater than 0.1 cm., up to 0.5 cm T1b: tumor greater than 0.5 cm., up to 1.0 cm. T1c: tumor greater than 1.0 cm., up to 2.0 cm. T2: tumor greater than 2.0 cm. & up to 5 cm. T3: tumor greater than 5.0 cm. in maximum size T4: tumor of any size that ALSO: T4a: either directly extends into chest-wall tissue (not including pectoralis muscle); or, T4b: directly extends into skin, showing edema (peau d orange), ulceration, or satellite nodules; or, T4c: is combined T4a and T4b; or, T4d: is inflammatory carcinoma, defined as diffuse brawny induration of the skin of the breast with an erysipeloid [red/dark & warm/ inflamed] edge, usually without an underlying palpable mass. REGIOAL LMPH ODE STATUS [] X: node status can not be (or has not been) assessed 0: negative lymph nodes p0: negative by H&E only p0(i-): H&E and IHC negative p0(i+): H&E neg and IHC pos; no ca. cell cluster bigger than 0.2 mm p0(mol-): H&E and molecular negative p0(mol+): H&E neg & molecular pos. 1: metastasis in movable ipsilateral axillary nodes p1: metastasis in 1-3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent p1mi: micrometastasis. >0.2, none >2 mm. p1a: metastasis in 1-3 axillary nodes p1b: metastasis in internal mammary nodes pic: metastasis in axillary and internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent 2: Metastasis in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis 2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures 2b: Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis P2: 4-9 positive axillary nodes; or, clinically positive internal mammary node (s) with neg. axillary p2a: 4-9 axillary pos. nodes, at least one metastasis being bigger than 2 mm p2b: positive clinically positive internal mammary node (s) with negative axillary nodes 3: Metastasis in ipsilateral infraclavicular lymph node (s) with or without axillary lymph node involvement, or in clinically apparent ipsilateral internal mammary lymph node (s) and in the presence of clinically evident axillary lymph node metastasis, or metastasis in ipsilateral supraclavicular lymph node (s) with or without axillary or internal mammary lymph node involvement 3a: Metastasis in ipsilateral infraclavicular lymph node (s) and axillary lymph node (s) 3b: Metastasis in ipsilateral internal mammary lymph node (s) and axillary lymph node (s) 3c: Metastasis in ipsilateral supraclavicular lymph node (s) P3: Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes p3a: 10 or more positive axillary nodes, with at least one deposit being larger than 2 mm; or, pos. infraclavicular node (s) p3b: clinically positive internal mammary nodes that are positive & in association with one or more positive axillary nodes; or, more than 3 positive axillary nodes plus clinically negative but microscopically positive internal mammary nodes detected by sentinel lymph node dissection. p3c: positive supraclavicular node (s)

6 DISTAT METASTASIS [M] MX: distant metastasis status can not be (or has not been) assessed M0: no positive evidence of distant metastasis M1: definite positive evidence of distant metastasis STAGE ASSIGMET STAGE T status STATUS M STATUS Stage 0 Tis 0 M0 Stage I T1 0 M0 Stage IIA T0 1 M0 T1 1 M0 T2 0 M0 Stage IIB T2 1 M0 T3 0 M0 T0 2 M0 T1 2 M0 Stage IIIA T2 2 M0 T3 1 M0 T3 2 M0 Stage IIIB T4 0 M0 T4 1 M0 T4 2 M0 Stage IIIC any T 3 M0 Stage IV any T any M1 Metastatic work-up Optional metastatic work-up for Stage I patients with symptoms and in Stage IIA, IIB, and IIIA Bone scan if with localized symptoms or elevated alkaline phosphatase or if T3, 1, M0. Abdominal + pelvis computed tomography scan, or sonography (indicated if elevated alkaline phosphatase, abnormal liver function tests, abdominal symptoms, abnormal physical examination of the abdomen or pelvis, or if T3, 1, M0) Chest imaging (if pulmonary symptoms are present) Indications for Endocrine Treatment Patients with positive ER/PR. Tamoxifen is given after chemotherapy. It is given in premenopausal and postmenopausal women. Aromatase inhibitors are given in postmenopausal women. Hormonal treatment is given for 5 years Indications for Chemotherapy eoadjuvant setting May be given in T2-T3, any, M0. Chemotherapy may be given in patients with big tumors in comparison to the breast who desire breast conserving surgery. Adjuvant setting Tumors > cm with poor prognostic factors including moderately/poorly differentiated, angiolymphatic invasion, high nuclear grade, and high histologic grade, chemotherapy is recommended. Tumors >1 cm. Presence of any positive lymph node. Metastatic setting Chemotherapy is warranted in patients with metastasis for palliation and to possibly decrease metastatic lesions. (There is insufficient data to recommend chemotherapy for patients >70 years old.) Indications for Radiotherapy >4 positive axillary lymph nodes Radiation therapy to whole breast with or without boost to tumor bed and supraclavicular area. Radiation therapy may be given to internal mammary nodes 1 3 positive axillary lymph nodes - Radiation therapy to whole breast with or without boost to tumor bed and supraclavicular area. Consider radiation therapy to supraclavicular area. Consider radiation therapy to internal mammary nodes. egative axillary lymph nodes but tumor is more than 5 cm or with positive margins Postchemotherapy radiation. Margin is <1 mm consider postoperative radiotherapy. Indications for Trastuzumab It is given in the adjuvant setting to patients with HER2 positive tumors which is >1 cm. It is given after chemotherapy. Trastuzumab is given for one year. Follow-up Evidence from randomized trials indicate that periodic follow-up with bone scans, liver sonography, chest radiographs, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations. 2-4 Even when these tests permit earlier detection of recurrent disease, patient survival is unaffected. 3 Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer. The frequency of follow-up and the appropriateness of screening tests after the completion of primary treatment for stage I to stage III breast cancer remain controversial. 41

7 Table 1: Risk Categories for Women with ode-egative Breast Cancer Low Risk intermediate Risk High Risk (has all listed factors) (risk classified between (has at least 1 listed factor) the other 2 categories) Tumor size <1 cm 1-2 cm >2 cm ER or PR Status positive positive positive Tumor grade grade 1 grade 1-2 grade 2-3 (ational Cancer Institute. Stage I, II, IIIA, and operable IIIC breast cancer. 2005) 5 Table 2: Adjuvant Systemic Treatment Options for Women with Axillary ode- egative Breast Cancer Patient Group Low Risk intermediate Risk High Risk Premenopausal, ER- one or Tamoxifen Tamoxifen plus chemo- Chemotherapy plus positive or PR-positive therapy, tamoxifen alone, tamoxifen, or ovarian or ovarian ablation ablation alone or with tamoxifen or GnRH alone or with tamoxifen Premenopausal, ER Chemotherapy negative or PR-negative Postmenopausal, ER- one or Tamoxifen Tamoxifen plus chemo- Tamoxifen plus chemopositive or PR-positive therapy, tamoxifen therapy, tamoxifen alone alone Postmenopausal, ER Chemotherapy negative, or PR-negative Older than 70 years one or Tamoxifen Tamoxifen alone, Tamoxifen Tamoxifen; consider plus chemotherapy chemotherapy if ERnegative or PR-negative (ational Cancer Institute. Stage I, II, IIIA, and operable IIIC breast cancer. 2005) 5 Table 3: Treatment Options for Women with Axillary ode-positive Breast Cancer Patient Group Premenopausal, ER-positive or PR-positive Premenopausal, ER-negative or PR-negative Postmenopausal, ER-positive or PR-positive Postmenopausal, ER-negative or PR-negative Older than 70 years Treatments Chemotherapy plus Tamoxifen Chemotherapy Tamoxifen plus chemotherapy, Tamoxifen alone Chemotherapy Tamoxifen alone; consider chemotherapy if receptor-negative (ational Cancer Institute. Stage I, II, IIIA, and operable IIIC breast cancer. 2005) 5 42

8 Adjuvant Treatments 6 Combination Chemotherapy Regimens on-trastuzumab Containing Regimens TAC (docetaxel/doxorubicin/cyclophosphamide Dose-dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel every 2 weeks AC (doxorubicin/cyclophosphamide) followed by weekly paclitaxel TC (docetaxel and cyclophosphamide) AC (doxorubicin/cyclophosphamide) FAC/CAF (fluorouracil/doxorubicin/cyclophosphamide) FEC/CEF (cyclophosphamide/epirubicin/fluorouracil) CMF (cyclophosphamide/methotrexate/fluorouracil) AC followed by doxetacel every 3 weeks EC (epirubicin/cyclophosphamide) Trastuzumab Containing Regimens AC followed by T + concurrent trastuzumab (doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab, various schedules) TCH (docetaxel, carboplatin, trastuzumab) Docetaxel + trastuzumab followed by FEC (fluorouracil/ epirubicin/cyclophosphamide) Chemotherapy followed by trastuzumab sequentially AC followed by docetaxel + trastuzumab References 1. Breast. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. ew ork, : Springer, 2002, pp Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA 271 (20): , Rosselli Del Turco M, Palli D, Cariddi A, et al.: Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. ational Research Council Project on Breast Cancer follow-up. JAMA 271 (20): , Khatcheressian JL, Wolff AC, Smith TJ, et al.: American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24 (31): , ational Cancer Institute. Stage I, II, IIIA, and operable IIIC breast cancer ational Comprehensive Cancer etwork. Clinical Practice Guidelines in Oncology. Breast cancer. Version Suggested Readings 1. Laudico AV, Esteban DB, Redaniel MTM, Mapua CA, Reyes, LM Philippine Cancer Facts and Estimates Tolentino RS. A Comprehensive Literature Review of Breast Cancer Among Females in the Philippines. Philipp J Surg Spec 63 (4): , Paguio SP, Pineda-Santos ML, Madrid MA, MD, Alcazaren EAS, Carnate JM, Faundo AC, Lim MCF, MD, Kho MRC, Tolentino RS, de la Rosa DW. Consensus Guidelines for the Standardization of Histopathologic Reporting of Breast Carcinoma by the Philippine Society of Pathologists Hormonal Treatment Tamoxifen Tamoxifen is given for five years or is shifted to other aromatase inhibitors to complete five years. Aromatase Inhibitors The three commonly used hormonal agents are the nonsteroidal aromatase inhibitors anastrazole and letrozole and the steroidal aromatase inactivator exemestane. They are not given to premenopausal women. Treatment using aromatase inhibitors/inactivator solely or in sequence with tamoxifen is generally accepted up to five years (total length of hormonal treatment). Regimens for Metastatic Disease 6 Chemotherapy Regimens CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil) FEC (fluorouracil/epirubicin/cyclophosphamide) AC (doxorubicin/cyclophosphamide) EC (epirubicin/cyclophosphamide) AT (doxorubicin/docetaxel; doxorubicin/paclitaxel) CMF (cyclophosphamide/methotrexate/fluorouracil) Docetaxel/capecitabine (The selection, dosing, and administration of anti-cancer agents and the management of associated toxicities are complex and are best handled by a competent oncologist. The doses and chemotherapy schedule is available in the website of the ational Comprehensive Cancer etwork of the United States.) l Sign up and open your clinic to the world. 43

9 Recommended Therapeutics The following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's reference, available drugs are listed under each therapeutic class. For drug information, please refer to the Philippine Drug Directory System (PPD, PPD Pocket Version, PPD Text, PPD Tabs). Cytotoxic Drugs itrogen Mustards Cyclophosphamide Biomedis Cyclophosphamide Biomedis Cyclophosphamide Injection Cytoxan Ledoxan Platinum Complexes Carboplatin Biovinate Carbosin Kemocarb aproplat Paraplatin Folate Antagonist Methotrexate Alltrex Zexate Drugmaker's Biotech Tamoxifen Fenahex Gynatam olvadex-d Zitazonium Hormones & Antagonists in Malignant Disease Anastrozole Arimidex Biomedis Anastrazole Letrozole Femara Letoripe Immunosuppressants Exemestane Aromasin Pyrimidine Antagonist Fluorouracil Biomedis Fluorouracil Fivoflu Fluonco Fluroblastin Capecitabine Xeloda Cytotoxic antibiotics Anthracyclines Doxorubicin A.D. Mycin Adriblastina RD Adrim Adrosal Biomedis Doxorubicin HCl Caelyx Doxorubin Epirubicin Anthracin E.P. Mycin Pharmorubicin Taxenes Docetaxel Biomedis Docetaxel Daxotel Doci Hentaxel Taxotere Paclitaxel Biomedis Paclitaxel Intaxel anoxel apro-tax Paclitaxin Paxus Taxol Monoclonal Antibodies Trastuzumab Herceptin Tamoxifen Biomedis Tamoxifen 44

Philippine Society of Medical Oncology

Philippine Society of Medical Oncology Unit 1418, 14/F, orth Tower, Cathedral Heights Bldg., St. Luke s Medical Center E. Rodriguez Sr. Avenue, Quezon City 1099, Philippines Telefax: (632) 721-9326/ 723-0101