Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers

Lynn C. Hartmann, Thomas A. Sellers, Daniel J Schaid, Thomas S. Frank, Cheryl L. Soderberg, Diana L. Sitta, Marlene H. Frost, Clive S. Grant, John H. Donohue, John E. Woods, Shannon K. McDonnell, Catherine Walsh Vockley, Amie Deffenbaugh, Fergus J Couch, Robert Brian Jenkins

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Abstract

Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

Original languageEnglish (US)
Pages (from-to)1633-1637
Number of pages5
JournalJournal of the National Cancer Institute
Volume93
Issue number21
StatePublished - Nov 7 2001

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BRCA2 Gene
BRCA1 Gene
Breast Neoplasms
Mutation
Prophylactic Mastectomy
Penetrance
Risk Reduction Behavior
Sequence Analysis
Electrophoresis
Cohort Studies
Retrospective Studies
Gels

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hartmann, L. C., Sellers, T. A., Schaid, D. J., Frank, T. S., Soderberg, C. L., Sitta, D. L., ... Jenkins, R. B. (2001). Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. Journal of the National Cancer Institute, 93(21), 1633-1637.

Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. / Hartmann, Lynn C.; Sellers, Thomas A.; Schaid, Daniel J; Frank, Thomas S.; Soderberg, Cheryl L.; Sitta, Diana L.; Frost, Marlene H.; Grant, Clive S.; Donohue, John H.; Woods, John E.; McDonnell, Shannon K.; Vockley, Catherine Walsh; Deffenbaugh, Amie; Couch, Fergus J; Jenkins, Robert Brian.

In: Journal of the National Cancer Institute, Vol. 93, No. 21, 07.11.2001, p. 1633-1637.

Research output: Contribution to journalArticle

Hartmann, LC, Sellers, TA, Schaid, DJ, Frank, TS, Soderberg, CL, Sitta, DL, Frost, MH, Grant, CS, Donohue, JH, Woods, JE, McDonnell, SK, Vockley, CW, Deffenbaugh, A, Couch, FJ & Jenkins, RB 2001, 'Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers', Journal of the National Cancer Institute, vol. 93, no. 21, pp. 1633-1637.
Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. Journal of the National Cancer Institute. 2001 Nov 7;93(21):1633-1637.
Hartmann, Lynn C. ; Sellers, Thomas A. ; Schaid, Daniel J ; Frank, Thomas S. ; Soderberg, Cheryl L. ; Sitta, Diana L. ; Frost, Marlene H. ; Grant, Clive S. ; Donohue, John H. ; Woods, John E. ; McDonnell, Shannon K. ; Vockley, Catherine Walsh ; Deffenbaugh, Amie ; Couch, Fergus J ; Jenkins, Robert Brian. / Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. In: Journal of the National Cancer Institute. 2001 ; Vol. 93, No. 21. pp. 1633-1637.
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title = "Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers",
abstract = "Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90{\%}. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5{\%}-100{\%} (95{\%} confidence interval = 41.4{\%} to 100{\%}). Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.",
author = "Hartmann, {Lynn C.} and Sellers, {Thomas A.} and Schaid, {Daniel J} and Frank, {Thomas S.} and Soderberg, {Cheryl L.} and Sitta, {Diana L.} and Frost, {Marlene H.} and Grant, {Clive S.} and Donohue, {John H.} and Woods, {John E.} and McDonnell, {Shannon K.} and Vockley, {Catherine Walsh} and Amie Deffenbaugh and Couch, {Fergus J} and Jenkins, {Robert Brian}",
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T1 - Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers

AU - Hartmann, Lynn C.

AU - Sellers, Thomas A.

AU - Schaid, Daniel J

AU - Frank, Thomas S.

AU - Soderberg, Cheryl L.

AU - Sitta, Diana L.

AU - Frost, Marlene H.

AU - Grant, Clive S.

AU - Donohue, John H.

AU - Woods, John E.

AU - McDonnell, Shannon K.

AU - Vockley, Catherine Walsh

AU - Deffenbaugh, Amie

AU - Couch, Fergus J

AU - Jenkins, Robert Brian

PY - 2001/11/7

Y1 - 2001/11/7

N2 - Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

AB - Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

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M3 - Article

VL - 93

SP - 1633

EP - 1637

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

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