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Bilateral breast cancer warrants BRCA testing: regardless of family history.

SAN ANTONIO -- Women with bilateral invasive breast cancer have a high prevalence of BRCA1 and BRCA2 mutations regardless of whether they possess a strong family history of breast or ovarian cancer, Alicia A. Parlanti reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Based upon this observation in a large new stud); women with bilateral invasive breast cancer--including those in whom the first and second diagnoses are separated by decades--ought to be offered genetic risk assessment services including BRCA mutation testing, said Ms. Parlanti of Myriad Genetic Laboratories in Salt Lake City.

She reported on 11,603 women with invasive breast cancer who underwent BRCA mutation testing at Myriad upon their physicians' orders. Among the subset of 1,565 women with a reported diagnosis of bilateral breast cancer, the prevalence of deleterious mutations was 25.4%. That rate is up to fivefold higher than in some prior reports in the literature; however, those earlier reports are unpersuasive because of very small sample sizes, she continued.

In her study, more than 10,000 women underwent analysis of the full BRCA sequence. The remaining 1,075 had a genetic analysis restricted to the three specific Ashkenazi Jewish founder mutations.

Among the 1,165 women with a diagnosis of bilateral invasive breast cancer before age 50, the prevalence of a deleterious BRCA mutation was 30.8%. That was significantly higher than the 9.5% rate among 400 women for whom the diagnosis of bilateral breast cancer came at age 50 or later.

In women without a family history of breast cancer before age 50 or ovarian cancer at any age, the prevalence of BRCA mutations was 13.5% among 460 women with bilateral breast cancer before age 50, a rate significantly higher than the 8.4% rate among 2,649 women with a diagnosis of unilateral breast cancer before age 50.

However, the BRCA mutation prevalence among women with bilateral breast cancer before age 50 but a negative family history was not significantly different from the 17.0% prevalence of BRCA mutations among women with a diagnosis of unilateral breast cancer before age 50 and with only one first- or second-degree relative with breast cancer prior to age 50.

Patients with bilateral breast cancer whose second diagnosis came within 20 years of the first had a higher prevalence of BRCA mutations than those with a second diagnosis 20-40 years following the first.

While bilateral breast cancer is fairly common, accounting for 13.5% of genetic testing requests in Ms. Parlanti's study, synchronous bilateral breast cancer is a different matter.

In a separate presentation at the meeting, Dr. Joseph P. Crowe focused on the Cleveland Clinic Foundation experience with synchronous bilateral breast cancer, which was present in 2% of a series of 3,692 patients with breast cancer.

Although this series didn't include BRCA mutation testing data, it did produce a number of clinically relevant findings, such as the fact that 54% of women with synchronous bilateral breast cancer presented with a palpable lump in at least one breast. And a majority of patients with synchronous bilateral breast cancer had a stage II or higher tumor in at least one breast.

The most common histologic Finding in patients with synchronous bilateral breast cancer, regardless of presentation, was infiltrating ductal carcinoma. Patients with infiltrating lobular carcinoma in one breast were not at increased likelihood of having the same histologic type of malignancy in the contralateral breast, said Dr. Crowe, chief of breast services at the clinic.

The average patient age in this series was 60 years regardless of whether they presented with a palpable lump or an abnormal mammogram.
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Author:Jancin, Bruce
Publication:Family Practice News
Date:Jan 1, 2004
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