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Modifiers of Risk

by Drea Thew

Presenter: Steven Narod, MD, Director of the Familial Breast Cancer Research Unit at the Centre for Research in Women’s Health, Toronto

Esteemed researcher Steven Narod, MD, the world’s most cited breast cancer researcher between 1994 and 2004, opened the conference with a presentation on “Modifiers of Risk in BRCA Carriers.”

He presented findings from his recent research on the risk-modifying influences of several factors on breast and ovarian cancer risk. His study population included 7,211 women from 11 countries over the age of 25 who had either a BRCA1 or BRCA2 mutation. Dr. Narod noted the effect of the following factors on breast and ovarian cancer risk.

Menarche

For both BRCA1 and BRCA2 carriers, the later the age of onset of menstruation, the lower the risk for breast cancer.

Oral Contraceptives

Oral contraceptives didn’t appear to increase breast cancer risk in BRCA2 carriers. Studying the age and duration of use of oral contraceptives on breast cancer risk in BRCA1 carriers, Dr. Narod found risk increased only in women who began taking the pill before age 30 or women who continued on contraceptives for three years or more. BRCA1 and BRCA2 carriers who took contraceptives for three years after age 30 had a substantially lower risk for ovarian cancer.

Pregnancy

Pregnancy affected BRCA1 and BRCA2 carriers differently. In BRCA2 carriers, more pregnancies were associated with higher breast and ovarian cancer risk. However, the increased breast cancer risk was statistically signifi cant ONLY after four births, and for ovarian cancer, significant ONLY after three births. In BRCA1 carriers more pregnancies were associated with lower risk for breast and ovarian cancer.The decreased risk was statistically significant for breast cancer ONLY after four births and for ovarian cancer ONLY after three births.

Breastfeeding

BRCA1 women who breastfed for at least 12 cumulative months had a lower risk for breast cancer and ovarian cancer. In women with BRCA2 mutations, breastfeeding was not associated with lowered risk for breast cancer. Although there was a lower risk for ovarian cancer in BRCA2 carriers who breastfed for at least a year, it was not statistically significant.

Oophorectomy

Oophorectomy performed before age 40 was associated with about a 60 percent reduction in breast cancer risk, in both BRCA1 and BRCA2 carriers. Oophorectomy between 40 and 45 was associated with a decreased breast cancer risk, but to a lesser degree than in the younger group. Estrogenonly replacement therapy (ERT) in previvors following oophorectomy did not counteract the protective effects of oophorectomy.

Tamoxifen

Although there is limited data on tamoxifen preventing a fi rst breast cancer in BRCA previvors, BRCA1 and BRCA2 carriers diagnosed with breast cancer who took tamoxifen had a decreased risk for a new diagnosis in the opposite breast.

Diet and Supplements

Dietary and supplement factors mentioned included coffee; DIM (diindolylmethane), an ingredient in cruciferous vegetables (broccoli, cabbage, Brussels sprouts, etc.); selenium, an essential trace element (Brazil nuts are the only reliable natural source); lycopene, found primarily in processed tomato products; and other sources of antioxidants such as pomegranates and green tea. Dr. Narod emphasized the lack of sufficient data to unequivocally state, “this is going to prevent cancer.”

Overview

Dr. Narod discussed the daily supplements and their dietary equivalents listed below.
(Editor’s note: some experts believe there is not sufficient data to support these recommendations, especially selenium):

Nutrient Supplement Dietary Equivalent
DIM 100 mg 3.5 lb cabbage or Brussels sprouts
Selenium 200-300 mcg None recommended (levels in food vary greatly by region)
Antioxidant 2.5 g green tea extract 10 8-oz cups (decaf)
Antioxidant Not yet available 1 whole pomegranate or
4 oz pomegranate juice
Lycopene 30-40 mg 2 glasses tomato juice (approx. 16 oz)

 

Dr. Narod’s risk management recommendations for BRCA1 and
BRCA2 carriers:

  • Weight control age 18-30
  • Selenium from age 20
  • DIM from age 30
  • Breast MRI annually from age 25
  • Breastfeeding for at least one year (cumulative)
  • Three years of oral contraceptives starting at age 30
  • Oophorectomy at age 35 followed by ERT (estrogen only)

Optional:

  • Bilateral mastectomy
  • Tamoxifen or Raloxifene for 5 years

Subcutaneous Mastectomy:

Dr. Narod noted that prophylactic mastectomy was chosen by about 25 percent of BRCA carriers in the US. The surgery lowers breast cancer risk by at least 98 percent—a standard that other risk management options simply can’t match. At Narod’s center, nipple-sparing mastectomy is recommended for its superior aesthetic results. This removes some of the objection for women who wouldn’t otherwise consider mastectomy, with a minimal increase in risk compared with simple mastectomy.

Reference

K Metcalfe, J Semple, S Narod. Time to Reconsider Subcutaneous Mastectomy for Breast-Cancer Prevention? The Lancet Oncology, June 2005; vol. 6, no 6: p. 431-434.

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