Two factors found to be associated with breast cancer recurrence

By Eve Harris

Women with the non-invasive form of breast cancer known as ductal carcinoma in situ (DCIS) are more likely to have a disease recurrence after treatment consisting of lumpectomy alone if:  their lesion was detected by palpation on physical exam, or it is of high nuclear grade.

DCIS accounts for 20 percent of all the newly diagnosed cases of breast cancer in the US. Its lesions by definition are restricted to the milk duct and do not invade the surrounding breast tissue. Treatment options include lumpectomy—with or without subsequent radiation therapy and with or without tamoxifen—and mastectomy.

In a study published in the November 19 Journal of the National Cancer Institute, researchers said high nuclear grade is strongly associated with an invasive cancer recurrence in women treated by lumpectomy alone. Nuclear grade is determined by a pathologist following a biopsy and describes the size and shape of the nucleus in a DCIS cell. Women whose DCIS was discovered by a physical exam, as opposed to a mammogram, and whose treatment consisted of a lumpectomy only, are also at relatively high risk of having an invasive cancer recurrence.

Principal Investigator Karla Kerlikowske, MD, UCSF associate professor of medicine and epidemiology and biostatistics, said this data will help women and their doctors make treatment decisions. “Not only did we identify indicators of risk, we ruled out a number of factors including family history, menopausal status and body mass index. In our study none of these factors that doctors traditionally assess at the time of a DCIS diagnosis proved to be a significant predictor of DCIS or invasive recurrence.” Kerlikowske treats patients at the San Francisco Veterans Affairs Medical Center.

Previous studies have failed to reach consensus on what characteristics predict recurrence of either DCIS or invasive cancer. This study of 1036 women in the greater San Francisco Bay Area was the largest of its kind:  a population-based study to measure both clinical and pathology characteristics for their relation to the recurrence of invasive cancer in those women with DCIS who had been treated by lumpectomy alone. According to its authors, it is also the first study to show that DCIS lesions detected by palpation and treated by lumpectomy alone are more likely to recur as invasive cancer than as DCIS.

The study participants were all aged 40 or older when diagnosed and were treated between January 1983 and December 1994. Those whose DCIS was detected by palpation on physical exam of the breast were at 12 percent risk of recurrence of invasive cancer within five years. The five-year risk of invasive cancer for those with mammogram-detected disease, about 80 percent in this study, was seven percent. Low nuclear grade corresponded to a risk of five percent within five years, as compared to 12 percent for women with high nuclear grade lesions.

“This suggests that women with palpable or high-nuclear grade DCIS lesions are at relatively high risk for recurrence of invasive cancer and may be appropriate candidates for adjuvant therapies beyond lumpectomy,” Kerlikowske said. Conversely, she said, women with low-nuclear-grade DCIS treated by lumpectomy alone can be informed that their chance of an invasive recurrence during the next five years is about one in 20.

The study was supported in part by the National Cancer Institute-funded UCSF Breast Cancer Specialized Program of Research Excellence, the California Breast Cancer Research Program and the NCI-funded Breast Cancer Surveillance Consortium.

Additional researchers are Annette Molinaro, University of California, Berkeley; Imok Cha, MD; Britt-Marie Ljung, MD; Virginia L. Ernster, PhD; Kim Stewart, MPH;  Karen Chew; Dan H. Moore II, PhD, and Fred Waldman, MD, PhD, all of UCSF.