Lynch Syndrome - is breast cancer a feature?

The debate on whether or not breast cancer is in the tumor spectrum for Lynch syndrome produces a conundrum for healthcare providers. The classic tumor spectrum for Lynch Syndrome (LS) includes colon, endometrial, ovarian, stomach, small intestine, hepatobiliary, urinary tract and brain/central nervous system cancers. Muir-Torre Syndrome (MTS) is a variant of LS that is associated with additional skin lesions including sebaceous gland tumors and keratoacanthomas. MTS was observed in 28% of LS families when assessing for MTS skin lesions [1]. It has also been reported that 10-14% of individuals with MTS present initially with breast cancer [2,3]. An extensive study published in 2002 excluded breast cancer as part of the tumor spectrum associated with LS [4]. However, more recently it was reported that DNA mismatch repair (MMR) gene deficiencies were identified in 51% of breast cancers arising in MMR mutation carriers [5]. Another study reported a male with an MLH1 mutation who had both colon and breast cancer. The breast cancer exhibited somatic reduction to homozygosity for the MLH1 mutation [6]. Here we report two unrelated families in which the proband has a germline MMR gene mutation and bilateral breast cancer, and one family in which the proband had ovarian and renal cancer and her daughter, maternal aunt and cousin had breast cancer at age 47, 59, and 48 respectively. This raises the question are these breast cancers associated with the MMR mutations or a breast cancer susceptibility gene and what testing should be offered?

References
South C, Hampel H, Comeras I, Westman J, Frankel W, Chapelle A: The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families. Journal National Cancer Institute 2008, 100:277-281.
Cohen P, Kohn S, Kurzrock R: Association of Sebaceous Gland Tumors and Internal Malignancy: The Muir Torre Syndrome. The American Journal of Medicine 1991, 90:606-613.
Cohen P, Kohn S, Davis D, Kurzrock R: The Muir Torre Syndrome. Dermatologic Clinics 1995, 13:79-89.
Muller A, Edmonston TB, Corao DA, et al.: Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer. Cancer Research 2002, 62:1014-1019.
Walsh M, Buchman D, Cummings M, Pearson S, Arnold S, Clendenning M, Wlaters R, McKeone D, Spurdle A, Hopper J, Jenkins M, Phillips K, Suthers G, George J, Goldblatt J, Muir A, Tucker K, Pelzer E, Gattas M, Woodall S, Parry S, Macrae F, Haile R, Baron J, Potter J, Marchand L, Bapat B, Thibodeau S, Lindor N, McGucklin M, Young J: Lynch Syndrome- Associated breast cancer: Clinicopathologic Characteristics of a Case Series from the Colon Cancer Family Registry. Clinical Cancer Research 2010, 16(7):2214-2224.
Boyd J, Rhei E, Federici M, Borgen P, Watson P, Franklin B, Karr B, Lynch J, Lemon S, Lynch H: Male breast cancer in hereditary nonpolyposis colorectal cancer syndrome. Breast cancer research and treatment 1999, 53:87-91

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Zohra AK Catts, Carrie Barnum, Marcie Parker, Chandra Somerman, Becky Grey and Bruce Boman

Source

Lynch Syndrome Linked to Breast, Pancreatic Cancers
A prospective study has confirmed that Lynch syndrome, an inherited disorder that predisposes to many types of cancer, significantly raises the risk of both breast cancer and pancreatic cancer.

The trial is the first to “find a strong association between breast cancer and Lynch syndrome,” said senior author and genetic epidemiologist Mark A. Jenkins, Ph.D., of the centre for molecular, environmental, genetic, and analytic epidemiology at the University of Melbourne.

Risk of breast cancer was fourfold higher for the Lynch syndrome patients, compared with the general population. The syndrome is known to increase the risk for a wide variety of other cancers, including colon cancer. Patients are typically advised to begin colonoscopies at an earlier age and repeat them more often than does the general population.

The new findings suggest that women with the syndrome might also benefit from enhanced breast cancer screening, but “further clarification of the risk of breast cancer for women at various ages is needed to determine the recommended age for mammography ... and to determine whether additional tests such as MRI are warranted,” Dr. Jenkins said.

The researchers also found an 11-fold increase in pancreatic cancers among the Lynch syndrome patients. Although elevated risk of this cancer has long been suspected, the evidence from previous studies has been inconsistent. The results were published online Feb. 13 in the Journal of Clinical Oncology.

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By: M. ALEXANDER OTTO,  Oncology Report Digital Network