TREATMENT OF BREAST CANCER; REVIEW AND UPDATES
AbstractCancer of the breast is the leading female cancer accounting for one fourth of the malignancies. The tumour remains the most researched, read and practiced upon around the Globe. The treatment has substantially improved breast cancer related outcomes, both for early as well as late stages with substantial improvements in disease free and overall survival. Therapeutic decisions not only rest on clinical & tumour characteristics, but also with the evolution of molecular biology and tissue microarray intrinsic sub-types have been found. Attempts are being made to translate therapy from genomic architecture of individual breast cancer. This facilitates customization of treatment avoiding un-necessary toxicity, costs and inconvenience. Optimizing treatment based on individual breast biology seems logical and allows unifying treatment. The paper reviews literature, incorporate updates and also describes immunohistochemistry based molecular classification: which are found simple to adapt, record, present and subsequently manage, summarizing clinical practices in management of these patients. Keywords: Breast; Cancer; Molecular biology; Triple negative; Immunohistochemistry; Receptor, erb-B2;Therapy; Antibodies, Monoclonal
Globocan 2012. Fact Sheets by Cancer [Internet]. [cited 2014 Dec 27]. Available from: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
American Cancer Society. Breast cancer facts and figures. [Internet]. [cited 2014 Dec 14]. Available from: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-042725.pdf
Ministry of Health Oman. Cancer Incidence Report Oman 2012. [Internet]. [cited 2014 Dec 14]. Available from: https://www.moh.gov.om/en/reports/Cancer%20Incidence%20in%20Oman%202010.pdf
Kumar S, Burney IA, Al-Ajmi A, Al-Moundhri MS. Changing Trends of Breast Cancer Survival in Sultanate of Oman. J Oncol 2011;316243.
Cancer of the Breast - SEER Stat Fact Sheets. [Internet]. [cited 2014 Dec 14]. Available from: http://seer.cancer.gov/statfacts/html/breast.html
Primary Breast Cancer: ESMO Clinical Practice Guidelines | ESMO [Internet]. [cited 2014 Dec 14]. Available from: http://www.esmo.org/Guidelines/Breast-Cancer/Primary-Breast-Cancer
National Comprehensive Cancer Network. Clinical practice guidelines vol 1. 2015. [Internet]. [cited 2016 Jan 14]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf
Litière S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, Van Limbergen E, et al. Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial. Lancet Oncol 2012;13(4):412–9.
Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. 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. Lancet 2005;366(9503):2087–106.
Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, et al. Locoregional recurrence after sentinel lymph node dissection with and without axillary dissection in patients with sentinel lymph node metastases. The American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010;252(3):426–32.
Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 2013;14(4):297–305.
Donker M, van Tienhoven G, Straver MF, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 2014;15(12):1303–10.
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. 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-B32 randomized phase III trial. Lancet Oncol 2010;11(10):927–33.
Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013;310(14):1455–61.
Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): A prospective, multicentre cohort study. Lancet Oncol 2013;14(7):609–18.
Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The Effect on Tumor Response of Adding Sequential Preoperative Docetaxel to Preoperative Doxorubicin and Cyclophosphamide: Preliminary Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27 . J Clin Oncol 2003;21(22):4165–74.
Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, et al. Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer. N Engl J Med 2009;360(20):2055–65.
Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, et al. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer. N Engl J Med 2008;358(16):1663–71.
Page DB, Naidoo J, McArthur HL. The 2014 San Antonio Breast Cancer Symposium: A successful lift-off for breast immunotherapy? NPJ Breast Cancer 2015;1:15001.
Lal P, Salazar PA, Ladanyi M, Chen B. Impact of polysomy 17 on HER-2/neu immunohistochemistry in breast carcinomas without HER-2/neu gene amplification. J Mol Diagn 2003;5(3):155–9.
Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet 2011;378(9804):1707–16.
Geyer Jr CE, Samuel JA, Wilson JW, Bandos H, Elledge RM, Robidoux A, et al. S3-02. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX. [Internet]. [cited 2014 Dec 31]. Available from: http://www.cancertherapyadvisor.com/breast-cancer-fec-100-not-superior-adriamycin-cyclophosphamide/article/387943/
Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010;362(22):2053–65.
Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiigione-Gertsch M, Price KN, et al. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node positive breast cancer. International Breast Cancer Study Group Trial 13-93. J Clin Oncol 2006;24(9):1332–41.
Higgins MJ, Liedke PE, Goss PE. Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial. Crit Rev Oncol Hematol 2013;86(1):23–32.
Pan K, Chlebowski RT. Adjuvant endocrine therapy of perimenopausal and recently postmenopausal women with hormone receptor-positive breast cancer. Clin Breast Cancer 2014;14(3):147–53.
Francis PA, Regan M, Fleming G. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): analysis of the SOFT trial. 2014;S3–8.
Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol 2007;25(22):3259–65.
Rakovitch E. Abstract #S5-04. Presented at: San Antonio Breast Cancer Symposium. [Internet]. [cited 2014 Dec 13]. Available from: http://www.medscape.com/viewarticle/754967
McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, et al. 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 2014;383(9935):2127–35.
Mukesk MB, Barnett GC, Wilkinson JS, Moody AM, Wilson C, Dorling L, et al. Randomized controlled trial of intensity-modulated radiotherapy for early breast cancer. 5-year results confirm superior overall cosmesis. J Clin Oncol 2013;31(6):4488–95.
Haertl PM, Pohl F, Weidner K, Groeger C, Koelbl O, Dobler B. Treatment of left sided breast cancer for a patient with funnel chest: volumetric-modulated arc therapy vs. 3D-CRT and intensity-modulated radiotherapy. Med Dosim 2013;38(1):1–4.
Abo-Madyan Y, Aziz MH, Aly MM, Schneider F, Sperk E, Clausen S, et al. Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer. Radiother Oncol 2014;110(3):471–6.
Kunkler IH, Canney P, Van Tienhoven G, Russell NS. Elucidating the role of chest wall irradiation in ‘intermediate-risk’ breast cancer: The MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol) 2008;20(1):31–4.
Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013;14(11):1086–94.
Agrawal RK, Alhasso A, Barrett-Lee PJ, Bliss JM, Bliss P, Bloomfield D, et al. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol 2011;100(1):93–100.
Perez EZ, Romond EH, Suman VJ. Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: Final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744–52.
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. 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 2013;24(9):2278–84.
Bachmann C, Schmidt S, Staebler A, Fehm T, Fend F, Schittenhelm J, Wallwiener D, et al. CNS metastases in breast cancer patients: prognostic implications of tumor subtype. Med Oncol 2015;32(1):400.
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (Neo-ALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012;379(9816):633–40.
Coleman R, Cameron D, Dodwell D, Bell R, Wilson C, Rathbone E, et al. Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial. Lancet Oncol 2014;15(9):997–1006.
Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger S, Menzel C, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Eng J Med 2009:360(7):679–91.
DeCensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, et al. Metformin and cancer risk in diabetic patients: a systemic review and metaanalyses. Cancer Prev Res (Phila Pa) 2010;3(11):1451–61.
Chlebowski RT, Blackburn GL. Final survival analysis from the randomized Women’s Intervention Nutrition Study (WINS) evaluating dietary intervention as adjuvant breast cancer therapy. Presented at: San Antonio Breast Cancer Symposium; December 9-13, 2014. [Internet]. [cited 19 Dec 2014]. Available from: http://www.onclive.com/conference-coverage/SABCS-2014/Women-With-Triple-Negative-Breast-Cancer-May-Reap-Greater-Survival-Benefit-From-Nutrition- Intervention#sthash.oQVSFGmO.dpuf
Pagani O, Regan MM, Walley BA, Colleoni GF, Lang I, Gomez HL, et al. Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer. N Engl J Med 2014;371(2):107–18.
Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiówka M, Hewson N, et al. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. J Clin Oncol 2015:23(32):3781–7.
Baselga J, Campone M, Piccart M, Burris III HA, Rugo HS, Sahmoud T, et al. Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer. N Engl J Med 2012;366(6):520–9.
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367(19):1783–91.
Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014;15(6):580–91.
Hurvitz SA, Andre F, Jiang Z, Shao Z, Neciosup SP, Mano MS, et al. Abstract S6-01: Phase 3, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: BOLERO-1; 2015.
Schnitt SJ. Will molecular classification replace traditional breast pathology? Int J Surg Pathol 2010;18(3 Suppl):S162–6.
Goldhirsch A, Wood WC, Coates AS, Gelbr RD, Thurlimann B, Senn HJ, et al. Strategies for subtypes dealing with the diversity of breast cancer. Highlights of the St. Gallen International expert Consensus on the primary therapy of early breast cancer. 2011. Ann Oncol 2011;22(8):1736–47.
Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: Intrinsic subtypes and signalling pathways. Cancer Treat Rev 2012;38(6):698–707.
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer. N Engl J Med 2004;351(27):2817–26.
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, et al. The genomic and transcriptomic architecture of 2000 breast tumors reveal novel subgroups. Nature 2012;486(7403):346–52.
Martin M, Segui MA, Anton A, Ruiz A, Ramos M, Adrover E, et al. Adjuvant Docetaxel for High-Risk, Node-Negative Breast Cancer. N Engl J Med 2010;363(23):2200–10.
Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 2005;23(16):3686–96.
Tolaney S, Barry W, Dang C, Yardley D, Moy B, Marcom P, et al. Abstract S1-04: A phase II study of adjuvant paclitaxel (T) and trastuzumab (H)(APT trial) for node-negative, HER2-positive breast cancer (BC); 2013.
Disis PL. Breast Cancer with High TIL Levels: Skip the Trastuzumab? 2014 Abstract bS1-06. [Internet]. [cited 2014 Dec 24]. Available from: http://www.medscape.com/viewarticle/836326?src=confwrap
Swain S, Kim S, Cortes J, Ro J, Semiglazov V, Campone M, et al. 350O_Prfinal overall survival (OS) analysis from the cleopatra study of first-line (1L) pertuzumab (PTZ), trastuzumab (T), and docetaxel (D) in patients (pts) with her2-positive metastatic breast cancer (MBC). Ann Oncol 2014;25(suppl_4).
Herold CI, anders CK. New targets for triple negative breast cancer. Oncology (Williston) 2013;27(9):846–54.
Byrski T, Gronwald J, Huzarski T, Dent R, Zuziak D, Wiśniowski R, et al. Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. In Springer, 2011; p.A4.
Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 2010;28(7):1145–53.
Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010;376(9737):235–44.
O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 2011;364(3):205–14.
Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, et al. Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. J Clin Oncol 2007;25(33):5210–17.
Denkert C, Minckwitz GV, Brase JC, Darb-Esfahani S, Gade S, Kronenwett R, et al. Expression of immunologic genes in triple-negative and HER2-positive breast cancer in the neoadjuvant GEPARSIXTO trial: Prediction of response to carboplatin-based chemotherapy. J Clin Oncol 2014;32(15 Suppl):510.
Sikov WM, Barry WT, Hoadley KA, Pitcher BN, Singh B, Tolaney SM, et al. Impact of intrinsic subtype by PAM50 and other gene signatures on pathologic complete response (pCR) rates in triple - negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) +/ - carboplatin (Cb) or bevacizumab (Bev): CALGB 40603/150709 (Alliance). 2014.
Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011;377(9769):914–23.
Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, et al. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol 2014;15(2):156–63.
Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490(7418):61–70.
Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121(7):2750–67.
Lehmann BD, Pietenpol JA. Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. J Pathol 2014;232(2):142–50.
Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 2013;19(19):5533–40.
Turner N, Biganzoli L, Malorni L, Migliaccio I, Moretti E, Pestrin M, et al. Adjuvant Chemotherapy: Which Patient? What Regimen. Am Soc Clin Oncol Educ Book 2013:3–8.
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