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Joanne Kotsopoulos,
Jan Lubinski,
Henry T Lynch,
Charmaine Kim-Sing,
Susan Neuhausen,
Rochelle Demsky,
William D Foulkes,
Parviz Ghadirian,
Nadine Tung,
Peter Ainsworth, [......],
Jeffrey Weitzel,
Dawna M Gilchrist,
Joanne L Blum,
Dana Zakalik,
Christian Singer,
Taya Fallen,
Ophira Ginsburg,
Tomasz Huzarski,
Ping Sun,
Steven A Narod
[show abstract]
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ABSTRACT: To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers.
We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates.
The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ = -0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (P(trend) < 0.0001) but not among BRCA2 (P(trend) ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; P(trend) < 0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P(trend) = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006).
These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer.
Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.
Cancer Epidemiology Biomarkers & Prevention 05/2012; 21(7):1089-96. · 4.12 Impact Factor
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Joanne Kotsopoulos,
Jan Lubinski,
Leonardo Salmena,
Henry T Lynch,
Charmaine Kim-Sing,
William D Foulkes,
Parviz Ghadirian,
Susan L Neuhausen,
Rochelle Demsky,
Nadine Tung, [......],
Leigha Senter,
Andrea Eisen, Charis Eng,
Christian Singer,
Ophira Ginsburg,
Joanne Blum,
Tomasz Huzarski,
Aletta Poll,
Ping Sun,
Steven A Narod
[show abstract]
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ABSTRACT: INTRODUCTION: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers. METHODS: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer. RESULTS: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43). CONCLUSIONS: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.
Breast cancer research: BCR 03/2012; 14(2):R42. · 5.24 Impact Factor
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Joanne Kotsopoulos,
Jan Lubinski,
Henry T Lynch,
Jan Klijn,
Parviz Ghadirian,
Susan L Neuhausen,
Charmaine Kim-Sing,
William D Foulkes,
Pal Moller,
Claudine Isaacs, [......],
S Merajver,
H Olsson,
D Provencher,
B Pasche,
G Evans,
W S Meschino,
E Lemire,
A Chudley,
D Rayson,
C Bellati
[show abstract]
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ABSTRACT: An early age at first full-term birth is associated with a reduction in the subsequent development of breast cancer among women in the general population. A similar effect has not yet been reported among women who carry an inherited BRCA1 or BRCA2 mutation. We conducted a matched case-control study on 1816 pairs of women with a BRCA1 (n = 1405) or BRCA2 (n = 411) mutation in an attempt to elucidate the relationship between age at first full-term pregnancy and the risk of developing breast cancer. Information about the age at first childbirth and other pregnancy-related variables was derived from a questionnaire administered to women during the course of genetic counselling. There was no difference in the mean age at first full-term birth in the cases and controls (24.9 years vs. 24.8 years; P = 0.81, respectively). Compared to women whose first child was born at or before 18 years of age, a later age at first full-term birth did not influence the risk of developing breast cancer (OR = 1.00 per year; 95% CI 0.98-1.03; P-trend = 0.67). Stratification by mutation status did not affect the results. These findings suggest that an early first full-term birth does not confer protection against breast cancer in BRCA mutation carriers. Nonetheless, BRCA mutation carriers opting for a prophylactic oophorectomy as a breast and/or ovarian cancer risk-reducing strategy should complete childbearing prior to age 40 when this prevention modality is most effective.
Breast Cancer Research and Treatment 11/2007; 105(2):221-8. · 4.43 Impact Factor
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Amy Finch,
Mario Beiner,
Jan Lubinski,
Henry T. Lynch,
Pal Moller,
Barry Rosen,
Joan Murphy,
Parviz Ghadirian,
Eitan Friedman,
William D. Foulkes, [......],
Babara Pasini,
Ruth Gershoni-Baruch, Charis Eng,
Olufunmilayo I. Olopade,
June McLennan,
Beth Karlan,
Jeffrey Weitzel,
Ping Sun,
Steven A. Narod,
for the Hereditary Ovarian Cancer Clinical Study Group
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ABSTRACT: Women with adverse mutations in the BRCA1 or BRCA2 gene are at an increased lifetime risk of ovarian cancer, and these mutations also increase vulnerability to cancers of the fallopian tube and peritoneum. Risk levels were examined in a prospective study based on data from an international registry comprising 32 centers in Canada, the United States, Europe, and Israel. The 1828 women identified as carrying a BRCA1 or BRCA2 mutation were followed up for a mean of 3.5 years. Participants had a mean age at entry of 47 years. Approximately three-fourths of the women carried a BRCA1 mutation and about one-fourth, a BRCA2 mutation; eight individuals carried both. Nearly one-third of women in the study (30.4%) had undergone bilateral salpingo-oophorectomy before entering the study, and another 38.5% had an oophorectomy during follow-up.
Fifty incident cancers were discovered during follow-up. Thirty-two of these cancers developed in women with intact ovaries. Eleven cancers were identified at the time of prophylactic oophorectomy, and 7 others after this procedure. The cumulative incidence of peritoneal cancer was estimated at 4.3% two decades after oophorectomy. The overall adjusted reduction in cancer risk associated with bilateral oophorectomy was 80%, with a multivariate hazard ratio of 0.2 and a 95% confidence interval of 0.07-0.58 (Fig. 1). The risk of ovarian, tubal, and primary peritoneal cancers in women with intact ovaries was highest for those 60-70 years of age who carried the BRCA1 mutation. Based on estimated incidence rates for women having both ovaries intact, the estimated penetrance of ovarian cancer was 62% up to age 75 years for carriers of the BRCA1 mutation, and 18% up to age 75 for those carrying the BRCA2 mutation.
Obstetrical and Gynecological Survey 12/2006; 62(1):29-31. · 2.51 Impact Factor
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Amy Finch,
Mario Beiner,
Jan Lubinski,
Henry T Lynch,
Pal Moller,
Barry Rosen,
Joan Murphy,
Parviz Ghadirian,
Eitan Friedman,
William D Foulkes, [......],
Mary Daly,
Babara Pasini,
Ruth Gershoni-Baruch, Charis Eng,
Olufunmilayo I Olopade,
Jane McLennan,
Beth Karlan,
Jeffrey Weitzel,
Ping Sun,
Steven A Narod
[show abstract]
[hide abstract]
ABSTRACT: Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort.
To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy.
Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up.
Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not.
The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates.
After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003).
Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.
JAMA The Journal of the American Medical Association 08/2006; 296(2):185-92. · 30.03 Impact Factor
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Eitan Friedman,
Joanne Kotsopoulos,
Jan Lubinski,
Henry T Lynch,
Parviz Ghadirian,
Susan L Neuhausen,
Claudine Isaacs,
Barbara Weber,
William D Foulkes,
Pal Moller, [......],
Beth Karlan,
Howard M Saal,
Judy E Garber,
Gad Rennert,
Dawna Gilchrist, Charis Eng,
Kenneth Offit,
Michael Osborne,
Ping Sun,
Steven A Narod
[show abstract]
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ABSTRACT: BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk of breast cancer in mutation carriers, but the effects of spontaneous and therapeutic abortions on the risk of hereditary breast cancer risk have not been well studied to date.
In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer.
There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio = 0.36; 95% confidence interval 0.16-0.83; p = 0.02).
Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers.
Breast cancer research: BCR 02/2006; 8(2):R15. · 5.24 Impact Factor
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André Nkondjock,
Parviz Ghadirian,
Joanne Kotsopoulos,
Jan Lubinski,
Henry Lynch,
Charmaine Kim-Sing,
Douglas Horsman,
Barry Rosen,
Claudine Isaacs,
Barbara Weber,
William Foulkes,
Peter Ainsworth,
Nadine Tung,
Andrea Eisen,
Eitan Friedman, Charis Eng,
Ping Sun,
Steven A Narod
[show abstract]
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ABSTRACT: Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffee consumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1-3, 4-5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72-1.12), 0.75 (95% CI 0.47-1.19) and 0.31 (95% CI 0.13-0.71; p-trend = 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk.
International Journal of Cancer 02/2006; 118(1):103-7. · 5.44 Impact Factor
