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Breast Cancer Research and Treatment

, Volume 142, Issue 1, pp 177–185 | Cite as

The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation

  • Adriana Valentini
  • Jan Lubinski
  • Tomasz Byrski
  • Parviz Ghadirian
  • Pal Moller
  • Henry T. Lynch
  • Peter Ainsworth
  • Susan L. Neuhausen
  • Jeffrey Weitzel
  • Christian F. Singer
  • Olufunmilayo I. Olopade
  • Howard Saal
  • Dominique Stoppa Lyonnet
  • William D. Foulkes
  • Charmaine Kim-Sing
  • Siranoush Manoukian
  • Dana Zakalik
  • Susan Armel
  • Leigha Senter
  • Charis Eng
  • Eva Grunfeld
  • Anna M. Chiarelli
  • Aletta Poll
  • Ping Sun
  • Steven A. NarodEmail author
  • The Hereditary Breast Cancer Clinical Study Group
Epidemiology

Abstract

Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan–Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31–1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.

Keywords

BRCA1 BRCA2 Breast cancer Pregnancy Survival 

Notes

Acknowledgments

The authors would like to acknowledge the study coordinators, Roxana Bucur Marcia Llacuachaqui, Alejandra Ragone, Jennifer Ng, Sara Elmi and Linda Steele. Supported by the Canadian Breast Cancer Foundation and the Women’s College Hospital. Also supported by NIH RO1CA74415 (S.L.N.) and P30 CA033752. S.L.N. is the Morris and Horowitz Families Endowed Professor. Recruitment of cases from the City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: J.W.) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The study conducted complies with the current laws of the country in which they were performed.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2013_2729_MOESM1_ESM.doc (26 kb)
Fig 4 (supplemental) Breast cancer-specific survival for subjects with and without a pregnancy: from ascertainment (DOC 25 kb)
10549_2013_2729_MOESM2_ESM.doc (26 kb)
Fig 5 (supplemental) Recurrence-free survival in subjects with and without a pregnancy after breast cancer: Follow-up from date of last birth (DOC 25 kb)

References

  1. 1.
    Hayat MJ, Howlader N, Reichman ME, Edwards BK (2007) Cancer statistics, trends, and multiple primary cancer analyses from the surveillance, epidemiology, and end results (SEER) program. Oncologist 12:20–37PubMedCrossRefGoogle Scholar
  2. 2.
    Petrek JA (1994) Breast cancer and pregnancy. J Natl Cancer Inst Monogr 16:113–121PubMedGoogle Scholar
  3. 3.
    Nugent P, O’Connell TX (1985) Breast cancer and pregnancy. Arch Surg 120:1221–1224PubMedCrossRefGoogle Scholar
  4. 4.
    Bonnier P, Romain S, Dilhuydy JM, Bonichon F, Julien JP, Charpin C, Lejeune C, Martin PM, Piana L (1997) Influence of pregnancy on the outcome of breast cancer: a case–control study. Societe Francaise de Senologie et de Pathologie Mammaire Study Group. Int J Cancer 72:720–727PubMedCrossRefGoogle Scholar
  5. 5.
    Rodriguez AO, Chew H, Cress R, Xing G, McElvy S, Danielsen B, Smith L (2008) Evidence of poorer survival in pregnancy-associated breast cancer. Obstet Gynecol 112:71–78PubMedCrossRefGoogle Scholar
  6. 6.
    Ali SA, Gupta S, Sehgal R, Vogel V (2012) Survival outcomes in pregnancy associated breast cancer: a retrospective case control study. Breast J 18:139–144PubMedCrossRefGoogle Scholar
  7. 7.
    Bladström A, Anderson H, Olsson H (2003) Worse survival in breast cancer among women with recent childbirth: results from a Swedish population-based register study. Clin Breast Cancer 4:280–285PubMedCrossRefGoogle Scholar
  8. 8.
    Guinee VF, Olsson H, Möller T, Hess KR, Taylor SH, Fahey T, Gladikov JV, van den Blink JW, Bonichon F, Dische S et al (1994) Effect of pregnancy on prognosis for young women with breast cancer. Lancet 343:1587–1589PubMedCrossRefGoogle Scholar
  9. 9.
    Azim HA Jr, Botteri E, Renne G, Dell’orto P, Rotmensz N, Gentilini O, Sangalli C, Pruneri G, Di Nubila B, Locatelli M, Sotiriou C, Piccart M, Goldhirsch A, Viale G, Peccatori FA (2012) The biological features and prognosis of breast cancer diagnosed during pregnancy: a case–control study. Acta Oncol 51:653–661PubMedCrossRefGoogle Scholar
  10. 10.
    Genin AS, Lesieur B, Gligorov J, Antoine M, Selleret L, Rouzier R (2012) Pregnancy-associated breast cancers: do they differ from other breast cancers in young women? Breast 4:550–555CrossRefGoogle Scholar
  11. 11.
    Ishida T, Yokoe T, Kasumi F, Sakamoto G, Makita M, Tominaga T, Simozuma K, Enomoto K, Fujiwara K, Nanasawa T et al (1992) Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: analysis of case–control study in Japan. Jpn J Cancer Res 83:1143–1149PubMedCrossRefGoogle Scholar
  12. 12.
    Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A (2010) Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J 16:76–82PubMedCrossRefGoogle Scholar
  13. 13.
    Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB, Koren G (1992) Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 166:781–787PubMedCrossRefGoogle Scholar
  14. 14.
    Dodds L, Fell DB, Joseph KS, Dewar R, Scott H, Platt R, Aronson KJ (2008) Relationship of time since childbirth and other pregnancy factors to premenopausal breast cancer prognosis. Obstet Gynecol 111:1167–1173PubMedCrossRefGoogle Scholar
  15. 15.
    Albrektsen G, Heuch I, Hansen S, Kvale G (2005) Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer 17:167–175CrossRefGoogle Scholar
  16. 16.
    Sankila R, Heinavaara S, Hakulinen T (1994) Survival of breast cancer patients after subsequent term pregnancy: “healthy mother effect”. Am J Obstet Gynecol 170:818–823PubMedCrossRefGoogle Scholar
  17. 17.
    Keilding N (2005) Delayed entry. In: Armitage P, Colton T (eds) Encyclopedia of biostatistics. Wiley, Hoboken, NJGoogle Scholar
  18. 18.
    Beadle BM, Woodward WA, Middleton LP, Tereffe W, Strom EA, Litton JK, Meric-Bernstam F, Theriault RL, Buchholz TA, Perkins GH (2009) The impact of pregnancy on breast cancer outcomes in women <or = 35 years. Cancer 115:1174–1184PubMedCrossRefGoogle Scholar
  19. 19.
    Blakely LJ, Buzdarm AU, Lozada JA, Shullaih SA, Hoy E, Smith TL, Hortobagyi GN (2004) Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer 100:465–469PubMedCrossRefGoogle Scholar
  20. 20.
    Von Schoultz E, Johansson H, Wilking N, Rutgvist LE (1995) Influence of prior and subsequent pregnancy on breast cancer prognosis. J Clin Oncol 13:430–434Google Scholar
  21. 21.
    Mueller BA, Simon MS, Deapen D, Kamineni A, Malone KE, Daling JR (2003) Childbearing and survival after breast carcinoma in young women. Cancer 98:1131–1140PubMedCrossRefGoogle Scholar
  22. 22.
    Mignot L (1989) Pregnancy after treated cancer of the breast. Results of a case–control. Pathol Biol (Paris) 37:1002Google Scholar
  23. 23.
    Hemminki K, Försti A, Sundquist J, Ji J (2008) Risk of familial breast cancer is not increased after pregnancy. Breast Cancer Res Treat 108:417–420PubMedCrossRefGoogle Scholar
  24. 24.
    Dalberg K, Eriksson J, Holmberg L (2006) Birth outcome in women with previously treated breast cancer—a population-based cohort study from Sweden. PLoS Med 3:e336PubMedCrossRefGoogle Scholar
  25. 25.
    Kroman N, Jensen MB, Melbye M, Wohlfahrt J, Mouridsen HT (1997) Should women be advised against pregnancy after breast-cancer treatment? Lancet 350:319–322PubMedCrossRefGoogle Scholar
  26. 26.
    Kroman N, Mouridsen HT (2003) Prognostic influence of pregnancy before, around, and after diagnosis of breast cancer. Breast 12:516–521PubMedCrossRefGoogle Scholar
  27. 27.
    Velentgas P, Daling JR, Malone KE, Weiss NS, Williams MA, Self SG, Mueller BA (1999) Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 85:2424–2432PubMedCrossRefGoogle Scholar
  28. 28.
    Ibrahim EM, Ezzat AA, Baloush A, Hussain ZH, Mohammed GH (2000) Pregnancy-associated breast cancer: a case–control study in a young population with a high-fertility rate. Med Oncol 17:293–300PubMedCrossRefGoogle Scholar
  29. 29.
    Keleher A, Wendt R III, Delpassand E, Stachowiak AM, Kuerer HM (2004) The safety of lymphatic mapping in pregnant breast cancer patients using Tc-99m sulfur colloid. Breast J 10:492–495PubMedCrossRefGoogle Scholar
  30. 30.
    Murphy CG, Mallam D, Stein S, Patil S, Howard J, Sklarin N, Hudis CA, Gemignani ML, Seidman AD (2012) Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer. Cancer 118:3254–3259PubMedCrossRefGoogle Scholar
  31. 31.
    Gelber S, Coates AS, Goldhirsch A, castiglione-Gertsch M, Marini G, Lindtner J, Edelmann DZ, Gudgeon A, Harvey V, Gelber RD, International Breast Cancer Study Group (2001) Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer. J Clin Oncol 19:1671–1675Google Scholar
  32. 32.
    Cooper DR, Butterfield J (1970) Pregnancy subsequent to mastectomy for cancer of the breast. Ann Surg 171:429–433PubMedCrossRefGoogle Scholar
  33. 33.
    Ives A, Saunders C, Bulsara M, Semmens J (2007) Pregnancy after breast cancer: population based study. BMJ 334:194PubMedCrossRefGoogle Scholar
  34. 34.
    Largillier R, Savignoni A, Gligorov J, Chollet P, Guilhaume MN, Spielmann M, Luporsi E, Asselain B, coudert B, Namer M, GET(N)A Group (2009) Prognostic role of pregnancy occurring before or after treatment of early breast cancer patients aged <35 years: a GET(N)A working group analysis. Cancer 115:5155–5165Google Scholar
  35. 35.
    Valachis A, Tsali L, Pesce LL, Polyzos NP, Dimitriadis C, Tsalis K, Mauri D (2010) Safety of pregnancy after primary breast carcinoma in young women: a meta-analysis to overcome bias of healthy mother effect studies. Obstet Gynecol Surv 65:786–793PubMedCrossRefGoogle Scholar
  36. 36.
    Azim HA Jr, Santoro L, Russell-Edu W, Pentheroudakis G, Pavlidis N, Peccatori FA (2012) Prognosis of pregnancy-associated breast cancer: a meta-analysis of 30 studies. Cancer Treat Rev 38:834–842PubMedCrossRefGoogle Scholar
  37. 37.
    Davies GA, Wolfe LA, Mottola MF, MacKinnon C, Society of Obstetricians and gynecologists of Canada, SOGC Clinical Practice Obstetrics Committee (2003) Joint SOGC/CSEP clinical practice guideline: exercise in pregnancy and the postpartum period. Can J Appl Physiol 28:330–341Google Scholar
  38. 38.
    Huzarski T, Byrski T, Gronwald J, Gorski B, Domagala P, Cybulski C, Oszurek O, Szwiec M, Gugala K, Stawicka M, Morawiec Z, Mierzwa T, Janiszewska H, Kilar E, Marczyk E, Kozak-Klonowska B, Siolek M, Surdyka D, Wisniowski R, Posmyk M, Sun P, Lubinski J, Narod SA, Polish Breast Cancer Consortium (2013) Ten year survival in BRCA1-negative and BRCA1-positive breast cancer patients. J Clin Oncol 31:3191–3196Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Adriana Valentini
    • 1
  • Jan Lubinski
    • 2
  • Tomasz Byrski
    • 2
  • Parviz Ghadirian
    • 3
  • Pal Moller
    • 4
  • Henry T. Lynch
    • 5
  • Peter Ainsworth
    • 6
  • Susan L. Neuhausen
    • 7
  • Jeffrey Weitzel
    • 8
  • Christian F. Singer
    • 9
  • Olufunmilayo I. Olopade
    • 10
  • Howard Saal
    • 11
  • Dominique Stoppa Lyonnet
    • 12
  • William D. Foulkes
    • 13
  • Charmaine Kim-Sing
    • 14
  • Siranoush Manoukian
    • 15
  • Dana Zakalik
    • 16
  • Susan Armel
    • 17
  • Leigha Senter
    • 18
  • Charis Eng
    • 19
    • 20
  • Eva Grunfeld
    • 21
  • Anna M. Chiarelli
    • 22
    • 23
  • Aletta Poll
    • 1
  • Ping Sun
    • 1
  • Steven A. Narod
    • 1
    • 22
    • 24
    Email author
  • The Hereditary Breast Cancer Clinical Study Group
  1. 1.Women’s College Research InstituteTorontoCanada
  2. 2.Hereditary Cancer CenterPomeranian Medical UniversitySzczecinPoland
  3. 3.Epidemiology Research Unit, Research Center of the University of Montreal Hospital Centre (CRCHUM)MontrealCanada
  4. 4.Research Group on Inherited Cancer, Department of Medical GeneticsOslo University HospitalRadiumhosptialetNorway
  5. 5.Department of Preventive Medicine and Public HealthCreighton University School of MedicineOmahaUSA
  6. 6.London Regional Cancer ProgramLondonCanada
  7. 7.Department of Population SciencesBeckman Research Institute of City of HopeDuarteUSA
  8. 8.City of Hope National Medical CenterDuarteUSA
  9. 9.Department of Obstetrics and Gynaecology and Comprehensive Cancer CenterMedical University of ViennaViennaAustria
  10. 10.Center for Clinical Cancer GeneticsUniversity of ChicagoChicagoUSA
  11. 11.Hereditary Cancer Program, Division of Human GeneticsChildren’s Hospital Medical CenterCincinnatiUSA
  12. 12.Service de Génétique OncologiqueInstitut Curie Hôpital, Institut Curie Centre de RechercheParisFrance
  13. 13.Department of Medical GeneticsMcGill UniversityMontrealCanada
  14. 14.BC Cancer AgencyVancouverCanada
  15. 15.Fondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  16. 16.Cancer Genetics ProgramBeaumont HospitalRoyal OakUSA
  17. 17.Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Princess Margaret HospitalUniversity of TorontoTorontoCanada
  18. 18.Division of Human GeneticsThe Ohio State University Medical CenterColumbusUSA
  19. 19.Genomic Medicine Institute and Center for Personalized Genetic HealthcareCleveland ClinicClevelandUSA
  20. 20.Department of Genetics and Genome Sciences and Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA
  21. 21.Department of Family and Community MedicineUniversity of TorontoTorontoUSA
  22. 22.Dalla Lana School of Public HealthUniversity of TorontoTorontoUSA
  23. 23.Cancer Care OntarioTorontoUSA
  24. 24.Women’s College Research InstituteTorontoCanada

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