Breast Cancer

  • Inês Monteiro
  • Teresa Alvarez
  • Jean-Yves Meuwly
  • Khalil Zaman


Breast cancer is not a single disease. It is highly heterogeneous in its molecular biology and natural evolution, impacting treatment response and prognosis. It is one of the most prevalent cancers worldwide with high impact on individual, social and economic levels. Nowadays, breast cancer treatment demands a multidisciplinary approach and the involvement of informed patients. Personalized breast cancer care should mean both considering the prognostic and predictive biomarkers of a single tumor and considering an individual patient’s preferences.


Breast cancer Biomarkers Targeted therapy 



Aromatase inhibitor


breast cancer


cyclin-dependent kinases 4/6


cyclin D1


computed tomography


estrogen receptor


endocrine therapy


gonadotropin-releasing hormone


human epidermal growth factor receptor 2


lymph node


monoclonal antibody


metastatic breast cancer


magnetic resonance imaging


no special type


ovarian function suppression


overall survival


poly-adenosine diphosphate-ribose polymerase inhibitor


pathological complete response


positron emission computed tomography


progression-free survival


progesterone receptor


selective estrogen receptor degrader


selective estrogen receptor modulator


sentinel lymph node


sentinel lymph node biopsy


tumor-infiltrating lymphocytes


tumor node metastasis


  1. 1.
    International Agency for Research on Cancer (2012) GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012Google Scholar
  2. 2.
    American Cancer Society (2015) Global cancer facts & figures, 3rd edn. American Cancer Society, AtlantaGoogle Scholar
  3. 3.
    Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang X-S et al (2015) Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 385(9972):977–1010CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sun Y-S, Zhao Z, Yang Z-N, Xu F, Lu H-J, Zhu Z-Y et al (2017) Risk factors and preventions of breast Cancer. Int J Biol Sci 13(11):1387–1397CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Prev Biomarkers 15(6):1159–1169CrossRefGoogle Scholar
  6. 6.
    Collaborators MWS (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362(9382):419–427CrossRefGoogle Scholar
  7. 7.
    Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH et al (2010) Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 304(15):1684–1692CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cancer CGoHFiB (1996) Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347(9017):1713–1727CrossRefGoogle Scholar
  9. 9.
    Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL et al (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372(23):2243–2257CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A (2010) Male breast cancer. Crit Rev Oncol Hematol 73(2):141–155CrossRefGoogle Scholar
  11. 11.
    Screening IUPoBC (2012) The benefits and harms of breast cancer screening: an independent review. Lancet 380(9855):1778–1786CrossRefGoogle Scholar
  12. 12.
    Miglioretti DL, Lange J, Van Den Broek JJ, Lee CI, Van Ravesteyn NT, Ritley D et al (2016) Radiation-induced breast cancer incidence and mortality from digital mammography screening: a modeling study. Ann Intern Med 164(4):205–214CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E et al (2015) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(suppl_5):v8–v30CrossRefGoogle Scholar
  14. 14.
    Network NCC (2017) NCCN clinical practice guidelines in oncology (NCCN guidelines®) breast cancer screening and diagnosis version 1.2017Google Scholar
  15. 15.
    Peccatori F, Azim H Jr, Orecchia R, Hoekstra H, Pavlidis N, Kesic V et al (2013) Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(suppl_6):vi160–vvi70PubMedGoogle Scholar
  16. 16.
    Cardoso F, Kataja V, Tjan-Heijnen V (2017) Essentials for clinicians on breast cancer. ESMO Press, LisbonGoogle Scholar
  17. 17.
    Tan AR (2016) Cutaneous manifestations of breast cancer. Semin Oncol 43(3):331–334CrossRefGoogle Scholar
  18. 18.
    Dubar S, Boukrid M, de Joliniere JB, Guillou L, Vo QD, Major A et al (2017) Paget’s breast disease: a case report and review of the literature. Fron Surg 4:51CrossRefGoogle Scholar
  19. 19.
    Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ et al (2017) Breast cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67(4):290–303CrossRefGoogle Scholar
  20. 20.
    Gospodarowicz MK, Brierley JD, Wittekind C (2017) TNM classification of malignant tumours. John Wiley & Sons, OxfordGoogle Scholar
  21. 21.
    Glück S (2017) Consequences of the convergence of multiple alternate pathways on the estrogen receptor in the treatment of metastatic breast cancer. Clin Breast Cancer 17(2):79–90CrossRefGoogle Scholar
  22. 22.
    de Paula Costa Monteiro I, Madureira P, De Vasconscelos A, Humberto Pozza D, Andrade de Mello R (2015) Targeting HER family in HER2-positive metastatic breast cancer: potential biomarkers and novel targeted therapies. Pharmacogenomics 16(3):257–271CrossRefGoogle Scholar
  23. 23.
    Mukohara T (2015) PI3K mutations in breast cancer: prognostic and therapeutic implications. Breast Cancer: Targets Ther 7:111Google Scholar
  24. 24.
    Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2(2):127–137CrossRefGoogle Scholar
  25. 25.
    Lakhani SR (2012) WHO classification of tumours of the breast. International Agency for Research on Cancer, LyonGoogle Scholar
  26. 26.
    Oliveira TM, Elias J, Melo AF, Teixeira SR, Salomão Filho C, Gonçalves LM et al (2014) Evolving concepts in breast lobular neoplasia and invasive lobular carcinoma, and their impact on imaging methods. Insights Imaging 5(2):183–194CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Sinn H-P, Kreipe H (2013) A brief overview of the WHO classification of breast tumors. Breast Care 8(2):149–154CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Silverstein MJ (2003) The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 186(4):337–343CrossRefGoogle Scholar
  29. 29.
    Gilcrease M. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer: Hammond MEH, Hayes DF, Dowsett M, et al (Univ of Utah School of Medicine, Salt Lake City; Washington Univ School of Medicine, St Louis, MO; American Society of Clinical Oncology, Alexandria, VA; et al) Arch Pathol Lab Med 134: 907–922, 2010 §. Breast Dis Year Book Q 21(4):336–337Google Scholar
  30. 30.
    Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH et al (2013) 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 31(31):3997–4013CrossRefGoogle Scholar
  31. 31.
    Penault-Llorca F, Radosevic-Robin N (2017) Ki67 assessment in breast cancer: an update. Pathology 49(2):166–171CrossRefGoogle Scholar
  32. 32.
    Curigliano G, Burstein HJ, P Winer E, Gnant M, Dubsky P, Loibl S et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 28(8):1700–1712CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Morigi C (2017) Highlights from the 15th St Gallen International Breast Cancer Conference 15–18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. Ecancermedicalscience 11:732CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci 98(19):10869–10874CrossRefGoogle Scholar
  35. 35.
    Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A (2012) Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev 38(6):698–707CrossRefGoogle Scholar
  36. 36.
    Eltahir Y, Werners LL, Dreise MM, van Emmichoven IAZ, Jansen L, Werker PM et al (2013) Quality-of-life outcomes between mastectomy alone and breast reconstruction: comparison of patient-reported BREAST-Q and other health-related quality-of-life measures. Plast Reconstr Surg 132(2):201e–209eCrossRefGoogle Scholar
  37. 37.
    Schoenfeld JD, Harris JR (2011) Abbreviated course of radiotherapy (RT) for breast cancer. Breast 20:S116–SS27CrossRefGoogle Scholar
  38. 38.
    Group EBCTC (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. Lancet 366(9503):2087–2106CrossRefGoogle Scholar
  39. 39.
    Group EBCTC (2011) 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 378(9804):1707–1716CrossRefGoogle Scholar
  40. 40.
    Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J et al (2015) Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol 16(1):47–56CrossRefGoogle Scholar
  41. 41.
    Vrieling C, van Werkhoven E, Maingon P, Poortmans P, Weltens C, Fourquet A et al (2017) Prognostic factors for local control in breast cancer after long-term follow-up in the EORTC boost vs no boost trial: a randomized clinical trial. JAMA Oncol 3(1):42–48CrossRefGoogle Scholar
  42. 42.
    McGale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M 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. Elsevier. Lancet Oncol 383(9935):2127–2135CrossRefGoogle Scholar
  43. 43.
    Donker M, Slaets L, Rutgers E (2015) Axillary lymph node dissection versus axillary radiotherapy in patients with a positive sentinel node: the AMAROS trial. Ned Tijdschr Geneeskd 159:A9302-AGoogle Scholar
  44. 44.
    Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J et al (2006) Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 24(30):4888–4894CrossRefGoogle Scholar
  45. 45.
    Blamey R, Pinder S, Ball G, Ellis I, Elston C, Mitchell M et al (2007) Reading the prognosis of the individual with breast cancer. Eur J Cancer 43(10):1545–1547CrossRefGoogle Scholar
  46. 46.
    Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N et al (2001) Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 19(4):980–991CrossRefGoogle Scholar
  47. 47.
    Wishart G, Bajdik C, Azzato E, Dicks E, Greenberg D, Rashbass J et al (2011) A population-based validation of the prognostic model PREDICT for early breast cancer. Eur J Surg Oncol 37(5):411–417CrossRefGoogle Scholar
  48. 48.
    Lumachi F, Luisetto G, MM Basso S, Basso U, Brunello A, Camozzi V (2011) Endocrine therapy of breast cancer. Curr Med Chem 18(4):513–522CrossRefGoogle Scholar
  49. 49.
    Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381(9869):805–816CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Pagani O, Regan MM, Walley B, Fleming GF, Colleoni M, Lang I, et al (2014) Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): joint analysis of IBCSG TEXT and SOFT trials. American Society of Clinical Oncology, AlexandriaGoogle Scholar
  51. 51.
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I et al (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371(2):107–118CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Moore HC, Unger JM, Phillips K-A, Boyle F, Hitre E, Porter D et al (2015) Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 372(10):923–932CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J et al (2009) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28(3):509–518CrossRefGoogle Scholar
  54. 54.
    de Azambuja E, Bedard PL, Suter T, Piccart-Gebhart M (2009) Cardiac toxicity with anti-HER-2 therapies-what have we learned so far? Target Oncol 4(2):77–88CrossRefGoogle Scholar
  55. 55.
    Group EBCTC (2015) Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 386(10001):1353–1361CrossRefGoogle Scholar
  56. 56.
    Masuda N, Lee S-J, Ohtani S, Im Y-H, Lee E-S, Yokota I et al (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376(22):2147–2159CrossRefGoogle Scholar
  57. 57.
    Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K et al (2006) Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer. Cancer 106(10):2095–2103CrossRefGoogle Scholar
  58. 58.
    Gianni L, Pienkowski T, Im Y-H, Tseng L-M, Liu M-C, Lluch A et al (2016) 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol 17(6):791–800CrossRefGoogle Scholar
  59. 59.
    Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios C et al (2017) 3rd ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol 28(1):16–33PubMedGoogle Scholar
  60. 60.
    Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35:3638–3646CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375(20):1925–1936CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Tripathy DSJ (2017) Ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized phase III MONALEESA-7 trial. San Antonio breast cancer conference, abstract GS2-05Google Scholar
  63. 63.
    Piccart M, Hortobagyi GN, Campone M, Pritchard K, Lebrun F, Ito Y et al (2014) Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann Oncol 25(12):2357–2362CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Swain SM, Kim S-B, Cortés J, Ro J, Semiglazov V, Campone M et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14(6):461–471CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Robson M, Im S-A, Senkus E, Xu B, Domchek SM, Masuda N et al (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533CrossRefGoogle Scholar
  66. 66.
    Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso M, Gilbert F et al (2016) Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol 27(suppl_5):v103–vv10CrossRefGoogle Scholar
  67. 67.
    Kornblum N, Manola J, Klein P, Ramaswamy B, Brufsky A, Stella P et al (2017) Abstract S1-02: PrECOG 0102: a randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in post-menopausal women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC) resistant to aromatase inhibitor (AI) therapy. AACR.
  68. 68.
    de la Cruz-Merino L, Chiesa M, Caballero R, Rojo F, Palazón N, Carrasco F et al (2017) Breast Cancer immunology and immunotherapy: current status and future perspectives. Int Rev Cell Mol Biol 331:1–53CrossRefGoogle Scholar
  69. 69.
    Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R et al (2016) Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol 34(21):2460–2467CrossRefGoogle Scholar
  70. 70.
    Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA et al (2013) Phase II trial of bicalutamide in patients with androgen receptor–positive, estrogen receptor–negative metastatic breast cancer. Clin Cancer Res 19(19):5505–5512CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O’Shaughnessy J et al (2018) Enzalutamide for the treatment of androgen receptor–expressing triple-negative breast cancer. J Clin Oncol 36(9):884–890CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Bonnefoi H, Grellety T, Tredan O, Saghatchian M, Dalenc F, Mailliez A et al (2016) A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol 27(5):812–818CrossRefGoogle Scholar
  73. 73.
    Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM et al (2013) Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol 31(17):2128–2135CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Curigliano G, Cardinale D, Suter T, Plataniotis G, De Azambuja E, Sandri MT et al (2012) Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Ann Oncol 23(suppl_7):vii155–vvii66PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Inês Monteiro
    • 1
  • Teresa Alvarez
    • 1
  • Jean-Yves Meuwly
    • 2
  • Khalil Zaman
    • 3
  1. 1.Institute of PathologyUniversity Hospital of Lausanne (CHUV)LausanneSwitzerland
  2. 2.Department of Diagnostic and Interventional RadiologyUniversity Hospital of Lausanne (CHUV) and University of Lausanne (UNIL)LausanneSwitzerland
  3. 3.Breast Center, Medical Oncology, Department of OncologyUniversity Hospital CHUVLausanneSwitzerland

Personalised recommendations