Jewish World Review May 24, 2002 / 13 Sivan, 5762




Breast density & the risk of breast cancer

By Robert A. Wascher, M.D., F.A.C.S.

http://www.NewsAndOpinion.com | An increased density of breast tissue, as seen on a mammogram, has been linked to a possible increase in the risk of developing breast cancer. What has not been very clear is the reason for this association. Some have hypothesized that the dense breast is more likely to obscure small cancers lurking within the breast at the time of mammography. Others have suggested that women with dense breasts might have an environmental or genetic predisposition that causes both the increased breast tissue density and the increased risk of developing breast cancer. However, there has not been good scientific data to support any of these hypotheses to date.

A study at the University of California at San Francisco carefully evaluated the mammographic density of women's breasts and then correlated these findings with the same patients' family history of breast cancer. In their analysis, they found a significantly increased incidence of breast cancer among the sisters and mothers of women with mammographically dense breasts (none of the mammography patients had breast cancer). This finding suggests that increased breast density might be associated with a greater risk of developing breast cancer due to genetic factors. In order to further clarify this conclusion, the next logical step would be to assess patients with increased breast density for either of the two known breast cancer-associated genes (BRCA1 and BRCA2).

BRCA2 GENE MUTATIONS & THE RISK OF BREAST CANCER

Currently, two gene mutations (BRCA1 and BRCA2) have been identified as genetic factors that increase the risk of breast cancer and ovarian cancer. However, only about 10% of breast cancer patients have a mutation of either of these genes. At the same time, the actual increase in the risk of breast cancer in the presence of either of these two mutated genes has been vigorously debated.

The University of Pennsylvania studied 226 BRCA2 mutation carriers in 84 families in order to accurately estimate the impact of this genetic mutation. They found that 64% of the affected women eventually developed breast cancer, and at an average age of 48 years. Of those women who developed breast cancer, 13% developed cancer in both breasts (though not necessarily at the same time), while 19% developed other types of cancer. Ovarian cancer was diagnosed in 18% of the BRCA2 mutation carriers, and at an average age of 57 years. In male BRCA2 carriers, breast cancer occurred in 26% of cases.

The likely incidence of these two cancers among BRCA2 carriers has previously been estimated by statistical methods. However, this BRCA2 carrier study is likely to be much more accurate (although the authors note that the relatively young age of the study patients might have resulted in an underestimation of the risk of ovarian cancer, which tends to occur somewhat later in life than breast cancer). Among the general population without BRCA1/BRCA2 mutations, the current incidence of breast cancer in women is about 11%, and about 0.1% for men, while the risk of ovarian cancer is about 1.5%. Women with a family history of breast, ovarian, colorectal or prostate cancer in multiple relatives should probably undergo testing for these two genes.

COX-2 & BREAST/LUNG CANCERS

I have previously reported on the experimental use of COX-2 blockers (e.g., Vioxx and Celebrex) to prevent and treat colorectal cancers. There is growing evidence that other types of cancers might benefit from the use of these anti-inflammatory medications as well.

Several studies reported on the detection of the COX-2 enzyme in both early and advanced breast cancers, suggesting a possible role for COX-2 inhibitors in the prevention and/or treatment of breast cancers. In the earliest type of breast cancer (ductal carcinoma in situ, or DCIS), COX-2 was present in a whopping of 85% of biopsy specimens, including the non-cancerous breast cells adjacent to the tumor cells. Further evaluation is therefore warranted to see if COX-2 inhibitors can actually prevent or treat breast cancer.

Lung cancer also frequently expresses the COX-2 enzyme, and at least one study showed that the increased presence of this enzyme in lung tumors was linked to cancers that behaved more aggressively than tumors that did not over-express COX-2.

MOLECULAR DETECTION OF TUMOR CELLS IN THE BLOOD & PROGNOSIS

I presented some of our own research at the John Wayne Cancer Institute as well. We evaluated 90 blood samples from 30 patients with melanoma that had spread to the lymph nodes. All patients had undergone complete surgical removal of all detectable tumors, and were enrolled in a melanoma vaccine study in the early 1990s.

The patients had blood drawn every month while receiving the vaccine, and these blood samples were then frozen for later analysis. Using an exquisitely sensitive technique (reverse transcriptase-polymerase chain reaction, or RT-PCR) that can detect a single tumor cell floating among millions of blood cells, we studied the blood samples collected from these 30 patients during the first 4 months of their vaccine treatment.

We found that patients with detectable traces of tumor cells in their blood samples, despite the absence of any detectable melanoma tumors in their body, had a three-fold increased risk of eventual recurrence of their melanoma, and of dying from melanoma. Furthermore, the detection of these so-called occult circulating tumor cells predicted recurrence and death from melanoma months, and in some cases, years later.

This was a significant finding, as the clinical importance of microscopic numbers of tumor cells in the blood, in the absence of detectable tumors anywhere else in the body, has been unclear, while previous RT-PCR studies of the blood have provided inconclusive or contradictory results. Further evaluation and optimization of this molecular diagnostic test at our institution is underway in a large scale study of melanoma patients at this time.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.

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© 2002, Dr. Robert A. Wascher