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Endocrine interventions in women with BRCA1/2 mutations

A systematic review

Endokrine Interventionen bei Frauen mit BRCA-1/2-Mutation

Ein systematisches Review

  • Review
  • Published:
Der Gynäkologe Aims and scope

Abstract

Background

One in eight women will be diagnosed with breast cancer and 5 % of all breast cancer cases are attributable to a mutation in BRCA1 or BRCA2. Lifetime risk of the general population is about 1.5 %. The probability of an underlying mutation depends on family history, histologic subtype and age at diagnosis. For healthy BRCA1/2 mutation carriers, ovarian cancer risk varies between 15 and 60 % depending of the mutation and modifying factors.

Objectives

The safety of endocrine interventions in BRCA1/2 mutation carriers has been investigated in numerous trials. In this article an update on the current knowledge on safety of oral contraception, hormone therapy and fertility treatment in BRCA1/2 mutation carriers is provided. Furthermore, options for primary prevention are discussed.

Materials and methods

A systematic search in the Medline literature database through PubMed using the terms “BRCA”, “famil*”, “breast cancer”, “ovarian cancer”, “oral contraception”, “fertility”, “fertility treatment”, “infertility”, “tamoxifen”, “raloxifene”, “chemoprevention”, “prevention”, “hormone”, “hormone treatment”, “hormone therapy”, “salpingo-oophorectomy” and “endocrine” was performed. Articles published between 1995 and 2015 were included.

Conclusions

Oral contraceptives seem to slightly increase the breast cancer risk of BRCA1/2 mutation carriers, but they also have a tremendous protective effect against ovarian cancer. Parity, breastfeeding and fertility treatment do not seem to influence cancer risk in these women. Hormone therapy should be offered after risk-reducing salpingo-oophorectomy to limit osteoporosis and cardiac mortality. Tamoxifen and raloxifene are effective for primary prevention of breast cancer in BRCA1/2 mutation carriers; however possible adverse effects must be considered.

Zusammenfassung

Hintergrund

Bei ca. 5 % aller Mammakarzinome kann eine BRCA1- oder BRCA2-Mutation nachgewiesen werden. Das Lebenszeitrisiko für ein Ovarialkarzinom liegt in der Allgemeinbevölkerung bei ca. 1,5 %. Bei gesunden Mutationsträgerinnen variiert das Erkrankungsrisiko in Abhängigkeit von der Mutation und weiterer modifizierender Faktoren und wird zwischen 15 und 60 % angegeben.

Ziele

Der Artikel gibt ein Update über den Stand der Wissenschaft bezüglich der Sicherheit oraler Kontrazeptiva, Hormontherapien und Fertilitätsbehandlungen bei BRCA1/2-Mutationsträgerinnen. Ferner werden Möglichkeiten der primären Prävention diskutiert.

Material und Methoden

Durchgeführt wurde eine systematische Suche in der „Medline“ Literaturdatenbank über „Pubmed“. Die Suchbegriffe lauteten “BRCA”, “famil*”, “breast cancer”, “ovarian cancer”, “oral contraception”, “fertility”, “fertility treatment”, “infertility”, “tamoxifen”, “raloxifene”, “chemoprevention”, “prevention”, “hormone”, “hormone treatment”, “hormone therapy”, “salpingo-oophorectomy” und “endocrine”. Berücksichtigt wurden zwischen 1995 und 2015 publizierte Artikel.

Ergebnisse und Diskussion

Orale Kontrazeptiva scheinen das Mammakarzinomrisiko BRCA1/2-Mutationsträgerinnen nur gering zu erhöhen, hervorzuheben ist der deutliche protektive Effekt für Ovarialkarzinome; Parität, Laktation und Fertilitätstherapie scheinen das Karzinomrisiko nicht negativ zu beeinflussen. Frauen nach risikoreduzierender bilateraler Adenektomie sollte bis zum Erreichen ihres natürlichen Menopausenalters eine Hormontherapie angeboten werden, um ihr Osteoporoserisiko und die kardiovaskuläre Mortalität zu senken. Tamoxifen und Raloxifen können im Einzelfall eine Option zur Primärprävention hereditärer Mammakarzinome sein, wobei deren Nebenwirkungen zu berücksichtigen sind.

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  1. Klinik und Lehrstuhl für Frauenheilkunde und Geburtshilfe, Universität Regensburg am Caritas-Krankenhaus St. Josef, Landshuter Str. 65, 93053, Regensburg, Deutschland

    Susanne Schüler-Toprak,  Stephan Seitz &  Olaf Ortmann

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  1. Susanne Schüler-Toprak
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  2. Stephan Seitz
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  3. Olaf Ortmann
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Correspondence to Susanne Schüler-Toprak.

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S. Schüler-Toprak, S. Seitz and O. Ortmann state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals performed by any of the authors.

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Schüler-Toprak, S., Seitz, S. & Ortmann, O. Endocrine interventions in women with BRCA1/2 mutations. Gynäkologe 49, 348–356 (2016). https://doi.org/10.1007/s00129-016-3864-7

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