Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers

Camilo Adem, Carol Reynolds, Cheryl L. Soderberg, Jeffrey M. Slezak, Shannon K. McDonnell, Thomas J. Sebo, Daniel J Schaid, Jeffrey L. Myers, Thomas A. Sellers, Lynn C. Hartmann, Robert Brian Jenkins

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Abstract

BACKGROUND. BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS. The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS. The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS. The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalCancer
Volume97
Issue number1
DOIs
StatePublished - Jan 1 2003

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Breast
Breast Neoplasms
Mutation
Control Groups
Mastectomy
Carcinoma in Situ
Research Design
Inborn Genetic Diseases
Neoplasms
Leukocytes
Immunohistochemistry
Carcinoma
Prophylactic Mastectomy
DNA

Keywords

  • Benign breast disease
  • BRCA1/2 mutation carrier
  • Pathology
  • Prophylactic mastectomy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. / Adem, Camilo; Reynolds, Carol; Soderberg, Cheryl L.; Slezak, Jeffrey M.; McDonnell, Shannon K.; Sebo, Thomas J.; Schaid, Daniel J; Myers, Jeffrey L.; Sellers, Thomas A.; Hartmann, Lynn C.; Jenkins, Robert Brian.

In: Cancer, Vol. 97, No. 1, 01.01.2003, p. 1-11.

Research output: Contribution to journalArticle

Adem, C, Reynolds, C, Soderberg, CL, Slezak, JM, McDonnell, SK, Sebo, TJ, Schaid, DJ, Myers, JL, Sellers, TA, Hartmann, LC & Jenkins, RB 2003, 'Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers', Cancer, vol. 97, no. 1, pp. 1-11. https://doi.org/10.1002/cncr.11048
Adem, Camilo ; Reynolds, Carol ; Soderberg, Cheryl L. ; Slezak, Jeffrey M. ; McDonnell, Shannon K. ; Sebo, Thomas J. ; Schaid, Daniel J ; Myers, Jeffrey L. ; Sellers, Thomas A. ; Hartmann, Lynn C. ; Jenkins, Robert Brian. / Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. In: Cancer. 2003 ; Vol. 97, No. 1. pp. 1-11.
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title = "Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers",
abstract = "BACKGROUND. BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS. The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS. The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7{\%}) compared with their matched control group (25{\%}) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33{\%}). None of the 11 deleterious mutation carriers from the bilateral cohort (0{\%}) had PFC compared with 36{\%} of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS. The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.",
keywords = "Benign breast disease, BRCA1/2 mutation carrier, Pathology, Prophylactic mastectomy",
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T1 - Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers

AU - Adem, Camilo

AU - Reynolds, Carol

AU - Soderberg, Cheryl L.

AU - Slezak, Jeffrey M.

AU - McDonnell, Shannon K.

AU - Sebo, Thomas J.

AU - Schaid, Daniel J

AU - Myers, Jeffrey L.

AU - Sellers, Thomas A.

AU - Hartmann, Lynn C.

AU - Jenkins, Robert Brian

PY - 2003/1/1

Y1 - 2003/1/1

N2 - BACKGROUND. BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS. The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS. The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS. The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.

AB - BACKGROUND. BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS. The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS. The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS. The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.

KW - Benign breast disease

KW - BRCA1/2 mutation carrier

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