Clinical Management of Hereditary Breast Cancer Syndromes

Article

Abstract

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.

Keywords

BRCA1 BRCA2 Breast cancer Ovarian cancer PARP Oophorectomy Mastectomy 

Abbreviations

CMF

cyclophosphamide, methotrexate and 5FU

CS

Cowden Syndrome

ER

estrogen receptor

HBOC

hereditary breast and ovarian cancer syndrome

HRT

hormone replacement therapy

LFL

Li Fraumeni-Like Syndrome

LFS

Li Fraumeni Syndrome

MRI

magnetic resonance imaging

OCP

oral contraceptive pills

OR

odds ratio

ORR

objective response rate

PARP

poly(ADP-ribose) polymerase

pCR

pathological complete response

PR

progesterone receptor

RRM

risk reducing bilateral mastectomy

RRSO

risk reducing salpingo-oophorectomy

SERMS

selective estrogen receptor modulators

Notes

Acknowledgements

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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

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

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