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Published: Sunday, March 06, 2011 - 12:59

Triple Negative Breast Cancer

There is a subtype of breast cancer which is negative for estrogen receptor, progesterone receptor, and the genetic mutation known as HER2. This so-called ‘triple-negative’ subtype accounts for 10% to 20% of all breast cancers.

It has now been reported that two of the largest studies to date looking at this triple-negative breast cancer have found that reproductive factors, specifically, pregnancy and multiple childbirth as well as obesity and lack of physical activity increase the risk for the disease. It is an established fact that pregnancy does reduce the risk of estrogen receptor positive breast cancer (the commonest type).

Both studies used data from more than 155,000 women enrolled in the Women Health's Initiative (WHI). In that cohort, 307 women were diagnosed with triple-negative breast cancer after a follow-up of 8 years, and 2610 were diagnosed with estrogen-receptor (ER)-positive breast cancer.

One study, looking at body size and physical activity, was published online March , 2011 in the journal Cancer Epidemiology, Biomarkers & Prevention; the other, looking at reproductive history, was published online February 23 in the Journal of the National Cancer Institute.

Obesity and lack of physical activity

In the first study, the researchers found that obese women had a 35% higher risk for triple-negative breast cancer than women with the lowest body mass index (BMI); in the second study, women who had never given birth had a 40% lower risk for the disease than those who had experienced a full-term pregnancy. Surprisingly, the number of births affected the risk for triple-negative breast cancer; women who had given birth to 3 or more children were at higher risk than women who had given birth to 1 child. High physical activity has been shown to reduce the risk of both triple negative and ER Positive breast cancer.

"Our results suggest that triple-negative breast cancer can be a very different disease from other subtypes, and studies that look at risk factors really need to take that into account," Dr. Amanda Phipps, the lead researcher said. The results suggest that although the hormonal changes of pregnancy make the breast less susceptible to ER-positive cancer, these mechanisms do not affect the risk for triple-negative disease, she noted. And the association between obesity and physical activity and triple-negative disease suggests that mechanisms other than hormonal levels influence the risk for this subtype of breast cancer, she added.

The study of obesity and physical activity found that women in the highest BMI quartile had a 1.35-fold increased risk for triple-negative breast cancer, compared with women in the lowest quartile (95% CI, 0.92 to 1.99); in contrast, women in the lowest quartile had a 1.39-fold increased risk for ER-positive breast cancer, compared with women in the highest quartile (95% CI, 1.22-1.58).

Nulliparity and breast cancer

In the study on reproductive factors, nulliparity (never had children) was linked to a decreased risk for triple-negative breast cancer (HR, 0.61; 95% CI, 0.37 to 0.97) but an increased risk for ER-positive breast cancer (HR, 1.35; 95% CI, 1.20 to 1.52). Although number of births was associated with an increased risk for triple-negative breast cancer in the study that looked at reproductive risk factors, it was inversely associated with the risk for ER-positive disease (HR for 3 or more births vs 1 birth, 0.88; 95% CI, 0.74 to 1.04).

The small number of women who developed triple-negative breast cancer was a limitation for both studies, and is most likely the reason that the findings on obesity and physical inactivity and risk for triple-negative breast cancer were not statistically significant, Dr. Phipps acknowledged.

Although both studies are among the largest studies ever done on triple-negative breast cancer, more research needs to be done to confirm the findings, Dr. Phipps said. "We'd also like to study the association between these risk factors and younger women," she added.

Dr. Phipps speculated that the findings on the association between pregnancy and an increased risk for triple-negative breast cancer might be due to an abnormal response of the breast to pregnancy. The researchers suggest that obesity and physical inactivity might increase the risk for triple-negative breast cancer by affecting insulin-like growth factors or inflammatory changes in the breast.

Pregnancy, multiple births and obesity: Risk factors for a type of breast cancer

By Dr Joe Kabyemela, MD