BRCA1/BRCA2 Germline Mutations in Locally Recurrent Breast Cancer Patients After Lumpectomy and Radiation Therapy: Implications for Breast-Conserving Management in Patients With BRCA1/BRCA2 Mutations
Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with...
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creator | TURNER, B. C HARROLD, E HAFFTY, B. G MATLOFF, E SMITH, T GUMBS, A. A BEINFIELD, M WARD, B SKOLNICK, M GLAZER, P. M THOMAS, A |
description | Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT.
Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences.
After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease.
In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing |
doi_str_mv | 10.1200/JCO.1999.17.10.3017 |
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Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences.
After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease.
In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.1999.17.10.3017</identifier><identifier>PMID: 10506595</identifier><language>eng</language><publisher>Baltimore, MD: American Society of Clinical Oncology</publisher><subject>Adult ; Age of Onset ; Biological and medical sciences ; BRCA2 Protein ; Breast Neoplasms - genetics ; Breast Neoplasms - radiotherapy ; Breast Neoplasms - surgery ; Female ; Genes, BRCA1 - genetics ; Germ-Line Mutation ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Mastectomy, Segmental ; Medical sciences ; Middle Aged ; Neoplasm Proteins - genetics ; Neoplasm Recurrence, Local - genetics ; Patient Care Planning ; Risk Assessment ; Transcription Factors - genetics ; Treatment Outcome ; Tumors</subject><ispartof>Journal of clinical oncology, 1999-10, Vol.17 (10), p.3017-3024</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-2b20f9bfaea5dccd25abe85f28da90d29782a1197b72f0839f8a6e10c3198b103</citedby><cites>FETCH-LOGICAL-c362t-2b20f9bfaea5dccd25abe85f28da90d29782a1197b72f0839f8a6e10c3198b103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1949168$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10506595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TURNER, B. C</creatorcontrib><creatorcontrib>HARROLD, E</creatorcontrib><creatorcontrib>HAFFTY, B. G</creatorcontrib><creatorcontrib>MATLOFF, E</creatorcontrib><creatorcontrib>SMITH, T</creatorcontrib><creatorcontrib>GUMBS, A. A</creatorcontrib><creatorcontrib>BEINFIELD, M</creatorcontrib><creatorcontrib>WARD, B</creatorcontrib><creatorcontrib>SKOLNICK, M</creatorcontrib><creatorcontrib>GLAZER, P. M</creatorcontrib><creatorcontrib>THOMAS, A</creatorcontrib><title>BRCA1/BRCA2 Germline Mutations in Locally Recurrent Breast Cancer Patients After Lumpectomy and Radiation Therapy: Implications for Breast-Conserving Management in Patients With BRCA1/BRCA2 Mutations</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT.
Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences.
After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease.
In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.</description><subject>Adult</subject><subject>Age of Onset</subject><subject>Biological and medical sciences</subject><subject>BRCA2 Protein</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - radiotherapy</subject><subject>Breast Neoplasms - surgery</subject><subject>Female</subject><subject>Genes, BRCA1 - genetics</subject><subject>Germ-Line Mutation</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Mastectomy, Segmental</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Patient Care Planning</subject><subject>Risk Assessment</subject><subject>Transcription Factors - genetics</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkc9uEzEQhy0EoqHwBEjIBwSnTW1vHdvc0hWUolRFURHcLK93nLjaf9i7oDwhr4WXrEoutmb0zW9G-hB6TcmSMkIuvhR3S6qUWlKxTL2cUPEELShnIhOC86doQUTOMirzH2foRYwPhNBLmfPn6IwSTlZc8QX6c7Ut1vRiehm-htDUvgV8Ow5m8F0bsW_xprOmrg94C3YMAdoBXwUwccCFaS0E_DWhqRvx2g2p3IxND3bomgM2bYW3pvL_svD9HoLpDx_wTdPX3s4LXBfmvKxINYRfvt3hW9OaHTTTsnTB44bvftjj04sfD32JnjlTR3g1_-fo26eP98XnbHN3fVOsN5nNV2zIWMmIU6UzYHhlbcW4KUFyx2RlFKmYEpIZSpUoBXNE5spJswJKbE6VLCnJz9G7Y24fup8jxEE3Plqoa9NCN0YtiJCSUZHA_Aja0MUYwOk--MaEg6ZET_508qcnf5qKqTf5S1Nv5vixbKA6mTkKS8DbGTAxaXEhOfDxP6cuFV3JhL0_Ynu_2__2AXRsksSUyvSD7U42_gVOlLJ6</recordid><startdate>19991001</startdate><enddate>19991001</enddate><creator>TURNER, B. 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Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Mastectomy, Segmental</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Patient Care Planning</topic><topic>Risk Assessment</topic><topic>Transcription Factors - genetics</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TURNER, B. C</creatorcontrib><creatorcontrib>HARROLD, E</creatorcontrib><creatorcontrib>HAFFTY, B. G</creatorcontrib><creatorcontrib>MATLOFF, E</creatorcontrib><creatorcontrib>SMITH, T</creatorcontrib><creatorcontrib>GUMBS, A. A</creatorcontrib><creatorcontrib>BEINFIELD, M</creatorcontrib><creatorcontrib>WARD, B</creatorcontrib><creatorcontrib>SKOLNICK, M</creatorcontrib><creatorcontrib>GLAZER, P. M</creatorcontrib><creatorcontrib>THOMAS, A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TURNER, B. C</au><au>HARROLD, E</au><au>HAFFTY, B. G</au><au>MATLOFF, E</au><au>SMITH, T</au><au>GUMBS, A. A</au><au>BEINFIELD, M</au><au>WARD, B</au><au>SKOLNICK, M</au><au>GLAZER, P. M</au><au>THOMAS, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRCA1/BRCA2 Germline Mutations in Locally Recurrent Breast Cancer Patients After Lumpectomy and Radiation Therapy: Implications for Breast-Conserving Management in Patients With BRCA1/BRCA2 Mutations</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>1999-10-01</date><risdate>1999</risdate><volume>17</volume><issue>10</issue><spage>3017</spage><epage>3024</epage><pages>3017-3024</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT.
Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences.
After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease.
In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.</abstract><cop>Baltimore, MD</cop><pub>American Society of Clinical Oncology</pub><pmid>10506595</pmid><doi>10.1200/JCO.1999.17.10.3017</doi><tpages>8</tpages></addata></record> |
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subjects | Adult Age of Onset Biological and medical sciences BRCA2 Protein Breast Neoplasms - genetics Breast Neoplasms - radiotherapy Breast Neoplasms - surgery Female Genes, BRCA1 - genetics Germ-Line Mutation Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Mastectomy, Segmental Medical sciences Middle Aged Neoplasm Proteins - genetics Neoplasm Recurrence, Local - genetics Patient Care Planning Risk Assessment Transcription Factors - genetics Treatment Outcome Tumors |
title | BRCA1/BRCA2 Germline Mutations in Locally Recurrent Breast Cancer Patients After Lumpectomy and Radiation Therapy: Implications for Breast-Conserving Management in Patients With BRCA1/BRCA2 Mutations |
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