Abstract
Breast cancer is the most common cancer in women and accounts for more than 250,000 cases in the USA alone. Although a poster child for predictive markers and targeted therapies, progress in treatment for this cancer has been slow. This is particularly true for new predictive biomarkers, and the number of routinely assessed predictive markers is restricted to estrogen, progesterone, and human epidermal growth factor receptors. Proliferation plays an important role in prognostication of ER+ tumors; however, its role in prediction is uncertain. Cell cycle (CDK4/CDK6) inhibitors such as palbociclib/ribociclib have been demonstrated to have a place in the management of ER+ cancers. HER2 positivity predicts for response to a number of anti-HER2 targeted therapies. Patients with BRCA1/BRCA2 mutations respond well to PARP inhibitor (PARPi; e.g., olaparib) therapy. The role of PARPi in other types of breast cancer remains to be established. The high prevalence of breast cancer and failure of standard of care therapies have resulted in intense focus on developing novel therapies including targeted therapies. A number of agents have been tried either in combination with endocrine therapy and/ or chemotherapy for the treatment of metastatic cancer.
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Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486(7403):346–52.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.
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.
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012;486(7403):353–60.
Singh JC, Jhaveri K, Esteva FJ. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development. Br J Cancer. 2014;111(10):1888–98.
Andre F, Hurvitz S, Fasolo A, Tseng LM, Jerusalem G, Wilks S, et al. Molecular alterations and everolimus efficacy in human epidermal growth factor receptor 2-overexpressing metastatic breast cancers: combined exploratory biomarker analysis from BOLERO-1 and BOLERO-3. J Clin Oncol. 2016;34(18):2115–24.
Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160–7.
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.
Kalimutho M, Parsons K, Mittal D, Lopez JA, Srihari S, Khanna KK. Targeted therapies for triple-negative breast cancer: combating a stubborn disease. Trends Pharmacol Sci. 2015;36(12):822–46.
Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008;26(22):3785–90.
Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.
Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.
Fehrenbacher L, Cecchini RS, Geyer CE, Rastogi P, Costantino JP, Atkins JN, et al. NSABP B-47 (NRG oncology): phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) -> weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk node-negative invasive breast cancer (IBC) expressing HER2 staining intensity of IHC 1+or 2+with negative FISH (HER2-Low IBC). Cancer Res. 2018;78(4).
Esposito A, Criscitiello C, Curigliano G. Highlights from the 14(th) St Gallen international breast cancer conference 2015 in Vienna: dealing with classification, prognostication, and prediction refinement to personalize the treatment of patients with early breast cancer. Ecancermedicalscience. 2015;9:518.
Leung SCY, Nielsen TO, Zabaglo L, Arun I, Badve SS, Bane AL, et al. Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration. NPJ Breast Cancer. 2016;2:16014.
Burgess A, Chia KM, Haupt S, Thomas D, Haupt Y, Lim E. Clinical overview of MDM2/X-targeted therapies. Front Oncol. 2016;6:7.
Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16(7):816–29.
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Badve, S. (2019). Predictive Biomarkers and Targeted Therapies in Breast Cancer. In: Badve, S., Kumar, G. (eds) Predictive Biomarkers in Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-95228-4_35
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DOI: https://doi.org/10.1007/978-3-319-95228-4_35
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