Radiation therapy may be safe after all for women with breast cancer gene mutations

October 23, 2000

U-M study shows no differences in side effect rates, and suggests similar recurrence rates

Women with breast cancer who carry a genetic mutation that heightens their risk of the disease might not have to fear having radiation therapy as previously thought, according to a new study led by University of Michigan researchers.

In fact, the results suggest, women with mutations of the BRCA 1 or 2 gene who had breast-conserving surgery after cancer diagnosis may get the same benefit from radiation therapy with no greater incidence of short- or long-term side effects as women with non-hereditary cancer. Some doctors have been concerned that in carriers of the BRCA 1 or 2 mutation, radiation's ability to damage DNA in normal breast tissue might outweigh its benefit in killing cancer cells.

U-M radiation oncologist Lori Pierce, M.D., the study's leader, will report on Oct. 24 at the annual meeting of the American Society for Therapeutic Radiation Oncology in Boston. Pierce and her colleagues from the U-M Comprehensive Cancer Center and several partner institutions published results of the same study in the October issue of the Journal of Clinical Oncology.

"With five years of followup data in hand, we see no increased incidence of skin fibrosis, pain, shortness of breath or other side effects, which suggests that DNA repair mechanisms are intact in BRCA 1 and 2 mutation carriers," says Pierce. "The fear of harm, based on laboratory findings that the BRCA gene product is linked to the cells' own repair system, may have unnecessarily prevented some women from getting the full range of therapeutic care."

The retrospective study also found similar high rates of survival, and low rates of cancer recurrence in the affected breast, for 71 women with the BRCA 1 or 2 mutations and 213 without a mutation who had similar diagnoses, surgical procedures and treatments.

But, Pierce cautions, the cancer recurrence data are based on only 5 years of follow-up. Data on how the women fared after 10 years, due to be available as early as spring of 2002, will be needed to say more certainly whether radiation therapy can continue to reduce the risk of cancer recurrence in the treated breast or the development of new cancers in the same breast.

As many as 10 percent of all breast cancer cases result from inherited factors, while the rest are thought to be sporadic, or non-hereditary. In recent years, scientists have pinned down two genes -- dubbed BRCA 1 and BRCA 2 -- that seem to account for most of the inherited cases.

Women who inherit a BRCA 1 or 2 mutation are known to have an increased risk -- as high as 55 to 60 percent by age 70 -- of developing breast or ovarian cancer, probably because they have no genetic "safety net." In other words, they have no extra normal copy to take over if their one normal copy in a single breast cell undergoes mutation and the cell produces an abnormal form of the protein encoded by the gene.

Even though scientists don't yet understand the exact workings of the proteins that BRCA 1 and 2 produce, they think they may be tied to the mechanisms cells use to repair damaged DNA. Hence, the controversy over treating these women with radiation.

Since radiation therapy can reduce a woman's chance of breast cancer recurrence from 35 to 40 percent to 10 percent after lumpectomy, the question is an important one. But physicians have worried that therapeutic radiation, no matter how carefully planned and delivered, could cause DNA damage in the remaining normal copy of BRCA 1 or 2 or that carriers of either mutation would show evidence of increased sensitivity to radiation following radiation treatment.

Pierce and her colleagues set out to test these hypotheses by studying the outcome of American and Canadian women with either a BRCA 1 or 2 mutation who underwent radiation following lumpectomy for early stage breast cancer.

The researchers compared those women's outcomes and complication rates with the same endpoints in closely matched women with non-hereditary forms of the disease. About half the women in each group had had chemotherapy as well as surgery and radiation.

Since the study was looking for differences in the incidence of any effects of radiation, not just cancer-causing effects, the researchers looked at the women's records to see how many side effects, or complications, they had experienced after their radiation treatments.

The results showed no differences in the low rates of short-term side effects between the BRCA mutation carriers and sporadic cancer patients. Both groups had similar incidence of skin redness and irritation, and a 1 to 2 percent rate of dry cough or shortness of breath and breast discomfort. No significant differences were observed either in the rates of long-term complications such as skin fibrosis, chronic shortness of breath or rib fractures.

Turning to cancer recurrence, the researchers found no significant differences in the rates at which cancer returned to the affected breast after five years of follow-up compared to the sporadic patients. For those whose cancer did come back in the same breast, additional treatment such as mastectomy kept it in check. As for the other breast, mutation carriers had a higher rate of cancer, as expected.

Finally, the researchers looked at survival after five years. Again, no difference turned up between the two groups in relapse-free survival, cause-specific survival, and overall survival.

Says Pierce, "While it's too soon to say that breast-conserving therapy results in long-term rates of cancer control in the treated breast in BRCA 1 or 2 carriers, it is clear that radiation is well-tolerated and can be safely given to women who carry either breast cancer mutation. Clinically indicated adjuvant radiotherapy shouldn't be omitted in carriers based on toxicity concerns."
-end-


University of Michigan Health System

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.