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Hereditary breast and ovarian cancer: review and future perspectives

Abstract

Breast cancer (BC) is the most frequent carcinoma in women. The cumulative risk for the disease is 10% up to the age of 80 years. A familial history of BC and ovarian cancer (OC) is a significant risk factor. Some 5–10% of all cases of BC and 25–40% of cases in patients under the age of 35 years have a hereditary origin. BRCA1/BRCA2 mutations are responsible for 3–8% of all cases of BC and 30–40% of familial cases. Ten percent of patients with OC have a genetic predisposition. About 80% of families with a history of OC have BRCA1 mutations, while 15% have BRCA2 mutations. Women at risk can receive counseling from interdisciplinary cancer genetics clinics, while those at high risk can receive genetic testing. Risk calculation programs can define the risks and assist in decision making for genetic testing and clinical options. Clinical options require information on the risks of the disease and its mutation status. Chemoprevention is currently a controversial topic, while the use of oral contraceptives can be regarded as reducing the risk for OC. Prophylactic mastectomy and bilateral ovariectomy are the only options that lead to a demonstrable reduction in risk, but they do, of course, affect the patient’s physical integrity. It is not currently known whether intensified early cancer detection is individually beneficial, but this is currently the option that is the least invasive and least burdensome to the patient. Although hereditary BC has different pathological characteristics and the BRCA mutation is an independent negative prognostic factor, there are currently no special treatment guidelines. Without adjuvant hormone therapy or chemotherapy, the overall survival in BRCA mutation carriers is reduced. Chemotherapy regimens involving platinum are particularly beneficial in the treatment of hereditary BC.

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Abbreviations

BC:

Breast cancer

BCDDP:

Breast Cancer Detection Demonstration Project

BCPT-P1:

Breast Cancer Prevention Trial, Phase 1

CASH:

Cancer and Steroid Hormone (study)

CI:

confidence interval

CORE:

Continuing Outcomes Relevant to Evista (study)

DCIS:

ductal carcinoma in situ

GISS:

Goserelin Ibandronate Screening vs Screening (study)

GnRH:

gonadotropin-releasing hormone

HLA:

human leukocyte antigen

HNPCC:

hereditary nonpolyposis colorectal carcinoma

IBIS:

International Breast Intervention Study

LCIS:

lobular carcinoma in situ

MRI:

magnetic resonance imaging

OC:

ovarian cancer

OR:

odds ratio

RR:

relative risk

SEER:

Surveillance, Epidemiology, and End Results (study)

SIR:

standardized incidence ratio

STAR:

Study of Tamoxifen and Raloxifene

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Lux, M.P., Fasching, P.A. & Beckmann, M.W. Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med 84, 16–28 (2006). https://doi.org/10.1007/s00109-005-0696-7

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Keywords

  • Hereditary breast cancer
  • Hereditary ovarian cancer
  • BRCA
  • Genetics
  • Risk calculation
  • Predictive genetic testing