Clinical Management of Hereditary Breast Cancer Syndromes

  • Amy S. Clark
  • Susan M. DomchekEmail author


Over the past 15 years there has been substantial improvement in the understanding of hereditary breast cancer. Germline genetic testing for mutations in BRCA1, BRCA2, PTEN and TP53 allows for the identification of individuals at increased risk for breast, ovarian and other cancers. Advances in screening, prevention and treatment have led to improved clinical management which is best defined for BRCA1 and BRCA2 mutation carriers. The addition of screening techniques such as breast magnetic resonance imaging has been shown to lead to earlier detection. Risk-reducing salpingo-oophorectomy leads to a reduction in the risk of both ovarian cancer and breast cancer and also is associated with an improvement in overall survival. BRCA1/2 mutation status may be applicable to systemic therapy decisions. Preclinical and early clinical research suggests that specific classes of chemotherapy may be more effective in mutation carriers. Finally, PARP inhibitors represent a novel therapeutic strategy that exploits the weaknesses of BRCA1/2-associated malignancies.


BRCA1 BRCA2 Breast cancer Ovarian cancer PARP Oophorectomy Mastectomy 



cyclophosphamide, methotrexate and 5FU


Cowden Syndrome


estrogen receptor


hereditary breast and ovarian cancer syndrome


hormone replacement therapy


Li Fraumeni-Like Syndrome


Li Fraumeni Syndrome


magnetic resonance imaging


oral contraceptive pills


odds ratio


objective response rate


poly(ADP-ribose) polymerase


pathological complete response


progesterone receptor


risk reducing bilateral mastectomy


risk reducing salpingo-oophorectomy


selective estrogen receptor modulators



This work was supported by the MacDonald Family Foundation to SMD.

Financial disclosures

Dr. Domchek has received clinical research funding from Astra-Zeneca


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Abramson Cancer CenterHospital of the University of PennsylvaniaPhiladelphiaUSA

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