Lynch syndrome-associated breast cancers: Clinicopathologic characteristics of a case series from the colon cancer family registry

Michael D. Walsh, Daniel D. Buchanan, Margaret C. Cummings, Sally Ann Pearson, Sven T. Arnold, Mark Clendenning, Rhiannon Walters, Diane M. McKeone, Amanda B. Spurdle, John L. Hopper, Mark A. Jenkins, Kerry D. Phillips, Graeme K. Suthers, Jill George, Jack Goldblatt, Amanda Muir, Kathy Tucker, Elise Pelzer, Michael R. Gattas, Sonja WoodallSusan Parry, Finlay A. Macrae, Robert W. Haile, John A. Baron, John D. Potter, Loic Le Marchand, Bharati Bapat, Stephen N Thibodeau, Noralane Morey Lindor, Michael A. McGuckin, Joanne P. Young

Research output: Contribution to journalArticle

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Abstract

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.

Original languageEnglish (US)
Pages (from-to)2214-2224
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number7
DOIs
StatePublished - Apr 1 2010

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Hereditary Nonpolyposis Colorectal Neoplasms
Colonic Neoplasms
Registries
DNA Mismatch Repair
Breast Neoplasms
Colorectal Neoplasms
Mutation
Neoplasms
Microsatellite Instability
Mitotic Index
Steroid Receptors
Progesterone Receptors
Age of Onset
Estrogen Receptors
Observational Studies
Research Design
Necrosis
Hormones
Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Walsh, M. D., Buchanan, D. D., Cummings, M. C., Pearson, S. A., Arnold, S. T., Clendenning, M., ... Young, J. P. (2010). Lynch syndrome-associated breast cancers: Clinicopathologic characteristics of a case series from the colon cancer family registry. Clinical Cancer Research, 16(7), 2214-2224. https://doi.org/10.1158/1078-0432.CCR-09-3058

Lynch syndrome-associated breast cancers : Clinicopathologic characteristics of a case series from the colon cancer family registry. / Walsh, Michael D.; Buchanan, Daniel D.; Cummings, Margaret C.; Pearson, Sally Ann; Arnold, Sven T.; Clendenning, Mark; Walters, Rhiannon; McKeone, Diane M.; Spurdle, Amanda B.; Hopper, John L.; Jenkins, Mark A.; Phillips, Kerry D.; Suthers, Graeme K.; George, Jill; Goldblatt, Jack; Muir, Amanda; Tucker, Kathy; Pelzer, Elise; Gattas, Michael R.; Woodall, Sonja; Parry, Susan; Macrae, Finlay A.; Haile, Robert W.; Baron, John A.; Potter, John D.; Le Marchand, Loic; Bapat, Bharati; Thibodeau, Stephen N; Lindor, Noralane Morey; McGuckin, Michael A.; Young, Joanne P.

In: Clinical Cancer Research, Vol. 16, No. 7, 01.04.2010, p. 2214-2224.

Research output: Contribution to journalArticle

Walsh, MD, Buchanan, DD, Cummings, MC, Pearson, SA, Arnold, ST, Clendenning, M, Walters, R, McKeone, DM, Spurdle, AB, Hopper, JL, Jenkins, MA, Phillips, KD, Suthers, GK, George, J, Goldblatt, J, Muir, A, Tucker, K, Pelzer, E, Gattas, MR, Woodall, S, Parry, S, Macrae, FA, Haile, RW, Baron, JA, Potter, JD, Le Marchand, L, Bapat, B, Thibodeau, SN, Lindor, NM, McGuckin, MA & Young, JP 2010, 'Lynch syndrome-associated breast cancers: Clinicopathologic characteristics of a case series from the colon cancer family registry', Clinical Cancer Research, vol. 16, no. 7, pp. 2214-2224. https://doi.org/10.1158/1078-0432.CCR-09-3058
Walsh, Michael D. ; Buchanan, Daniel D. ; Cummings, Margaret C. ; Pearson, Sally Ann ; Arnold, Sven T. ; Clendenning, Mark ; Walters, Rhiannon ; McKeone, Diane M. ; Spurdle, Amanda B. ; Hopper, John L. ; Jenkins, Mark A. ; Phillips, Kerry D. ; Suthers, Graeme K. ; George, Jill ; Goldblatt, Jack ; Muir, Amanda ; Tucker, Kathy ; Pelzer, Elise ; Gattas, Michael R. ; Woodall, Sonja ; Parry, Susan ; Macrae, Finlay A. ; Haile, Robert W. ; Baron, John A. ; Potter, John D. ; Le Marchand, Loic ; Bapat, Bharati ; Thibodeau, Stephen N ; Lindor, Noralane Morey ; McGuckin, Michael A. ; Young, Joanne P. / Lynch syndrome-associated breast cancers : Clinicopathologic characteristics of a case series from the colon cancer family registry. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 7. pp. 2214-2224.
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abstract = "Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51{\%}) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51{\%} of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.",
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T1 - Lynch syndrome-associated breast cancers

T2 - Clinicopathologic characteristics of a case series from the colon cancer family registry

AU - Walsh, Michael D.

AU - Buchanan, Daniel D.

AU - Cummings, Margaret C.

AU - Pearson, Sally Ann

AU - Arnold, Sven T.

AU - Clendenning, Mark

AU - Walters, Rhiannon

AU - McKeone, Diane M.

AU - Spurdle, Amanda B.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Phillips, Kerry D.

AU - Suthers, Graeme K.

AU - George, Jill

AU - Goldblatt, Jack

AU - Muir, Amanda

AU - Tucker, Kathy

AU - Pelzer, Elise

AU - Gattas, Michael R.

AU - Woodall, Sonja

AU - Parry, Susan

AU - Macrae, Finlay A.

AU - Haile, Robert W.

AU - Baron, John A.

AU - Potter, John D.

AU - Le Marchand, Loic

AU - Bapat, Bharati

AU - Thibodeau, Stephen N

AU - Lindor, Noralane Morey

AU - McGuckin, Michael A.

AU - Young, Joanne P.

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N2 - Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.

AB - Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor-negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.

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