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Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy

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Abstract

Long term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast cancer (BCS), distant disease free survival (DDFS), and local recurrence free survival (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95% CI 0.41–0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40–0.85; p = 0.005), with a consistent but not statistically significant effect in LRFS. This effect was not seen in familial cases (HR > 1.0), and family history was found to interact with HT in BCS (p(interaction) = 0.0067) (BC-death) and DDFS (p(interaction) = 0.0070). There was phenotypic heterogeneity between HT-associated tumors in familial and non-familial cases, particularly on estrogen receptor (ER) status, although the interaction between HT and family history appears to be at least partially independent of these markers (p = 0.0370 after adjustment for standard prognostic factors). If confirmed by further studies, our results suggest that family history should be taken into consideration in clinical counseling before beginning a HT regimen.

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Acknowledgements

The authors would like to thank research nurse Virpi Palola and Dr. Hanna Peurala for data collection. The Finnish Cancer registry is gratefully acknowledged for the cancer diagnostic and follow-up data and The National Medical Reimbursement Registry of the Social Insurance Institution is acknowledged for the data on HT usage. This work was supported by the Helsinki University Hospital Research Fund, the Sigrid Juselius Foundation, the Finnish Cancer Society and the Academy of Finland [266528].

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, PO Box 700, 00029 HUS,, Helsinki, Finland

    Rainer Fagerholm, Kirsi Aaltonen, Mervi Halttunen-Nieminen & Heli Nevanlinna

  2. Department of Oncology, Helsinki University Hospital and University of Helsinki, PO Box 180, 00029 HUS,, Helsinki, Finland

    Maria Faltinova & Carl Blomqvist

  3. Department of Clinical Genetics, Helsinki University Hospital and University of Helsinki, PO Box 160, 00029 HUS,, Helsinki, Finland

    Kirsi Aaltonen & Kristiina Aittomäki

  4. Department of Pathology, Helsinki University Hospital, PO Box 400, 00029 HUS,, Helsinki, Finland

    Päivi Heikkilä

  5. Department of Oncology, Örebro University Hospital, S70185, Örebro, Sweden

    Carl Blomqvist

Authors
  1. Rainer Fagerholm
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  2. Maria Faltinova
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  3. Kirsi Aaltonen
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  4. Kristiina Aittomäki
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  6. Mervi Halttunen-Nieminen
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  7. Heli Nevanlinna
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Contributions

RF prepared the manuscript and performed most of the statistical analyses. MF classified the treatment data and patient material, performed initial statistical analyses. KA assisted in manuscript preparation. KA coordinated clinical case data acquisition from the Department of Clinical Genetics. PH reviewed the histopathological and immunohistochemical data. MH assisted in manuscript preparation and interpretation of the statistical findings in a clinical context. HN coordinated and supervised the study, participated in study design. CB designed the study, coordinated and supervised the study. All authors participated in the interpretation of the results and the preparation of the final manuscript.

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Correspondence to Heli Nevanlinna.

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Fagerholm, R., Faltinova, M., Aaltonen, K. et al. Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy. Familial Cancer 17, 321–331 (2018). https://doi.org/10.1007/s10689-017-0046-2

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