Breast cancer research delves into post-APBI complications, disease risk in black women

Jun 5, 2006

Two new studies take a closer look at the epidemiology of breast cancer, as well as a potential complication of treating the disease. First, East Coast investigators reported on the causes of persistent seroma after intraoperative placement of an accelerated partial-breast irradiation (APBI) device.

Then, a North American group of researchers found that certain breast cancer subtypes are more prevalent in African-American women, leading to a poorer disease prognosis.

Timing APBI

The MammoSite (Cytc, Marlborough, MA) applicator is commonly used in high-dose-rate APBI. But intraoperative placement of this device at the sites of tumor lumpectomy or re-excision can lead to complications, especially if APBI is performed too soon after surgery, according to Dr. David Wazer and colleagues in the International Journal of Radiation Oncology, Biology, Physics.

"The overall incidence of seroma formation after APBI with the MammoSite catheter may be underestimated in current clinical practice," the group wrote. "Placing the catheter in a fresh surgical wound (and subsequent irradiation) may significantly influence the cellular mechanisms of wound healing" (IJROBP, June 2006, Vol. 65:2, pp. 333-339).

For this study, Wazer, who is from Tufts-New England Medical Center in Boston, and colleagues included 38 patients who underwent intraoperative MammoSite placement between 2002 and 2005, either at Tufts or at the Rhode Island Hospital in Providence.

Patients underwent daily CT monitoring to verify balloon integrity and dosimetry. The device was removed after the prescribed dose of 35 Gy in 10 fractions, twice daily, was reached. Treatment was delivered using a high-dose-rate brachytherapy source of iridium-192, the authors said. Follow-up was performed one week after placement and then at one- to four-month intervals. Mammograms were obtained at six months and one year post-treatment.

The median follow-up time was 17 months, according to the results. The overall rate of seroma formation at any point after MammoSite placement was 76.3%. Persistent seroma (more than six months of follow-up) was seen in 68.4% of the patients. Of these, 46% experienced discomfort in the breast. Seroma was associated with a suboptimal cosmetic outcome.

"Aspiration was performed in 38.5% of patients with persistent seroma and resulted in near-immediate reaccumulation of fluid in all cases," the authors explained. "Three patients required biopsy or excision."

The group suggested the following factors may predict the risk for persistent seroma:

Body mass index
Total amount of tissue removed during surgery
Patient age
Electrocautery in place of scalpel dissection

However, the most important factor was the actual timing of the catheter placement. When the catheter is deployed less than a week after surgery, "it is likely that this practice results in perturbation of the normal wound healing mechanism that would not have been seen if both catheter insertion and irradiation were delayed for >1 week after lumpectomy," they stated.

Fortunately, the authors found that dose homogeneity and maximal dose were not associated with seroma formation. Also, postimplant infection was significantly associated with a reduced risk of persistent seroma, which may change the wound environment enough to act as an inflammatory mediator, they said.

The authors pointed out that the American Society of Breast Surgeons (ASBS) and the current multidisciplinary trial, the National Surgical Adjuvant Bowel and Breast Project, call for postoperative placement of any brachytherapy system. The ASBS guidelines recommend a delay of at least one week.

Beyond BRCA

It's well known that women who carry BRCA mutations are at a greater risk for breast cancer. Evidence also backs up the reality that, genetics notwithstanding, breast cancer among African-American women is characterized by a higher grade, later stage and diagnosis, and worse survival outcomes.

Is there a connection between African-American race and genetic risk for breast cancer? Dr. Lisa Carey from the University of North Carolina (UNC) in Chapel Hill set out to answer that question with a gene expression analysis of population-based breast cancer subtypes.

"The Carolina Breast Cancer Study (CBCS) is a population-based, case-control study of environmental and molecular determinants of breast cancer risk," wrote Carey's group in the Journal of the American Medical Association. "The CBCS is unique in that it oversampled African-American and premenopausal women," an important factor because mortality among black women under age 50 is 77% compared to white women, they added (JAMA, June 7, 2006, Vol. 295:21, pp. 2492-2502).

Carey is from the UNC division of hematology/oncology. Her co-authors are from the UNC departments of medicine, genetics, pathology, public health, and epidemiology. Other contributors are from Duke University in Durham, NC; the University of British Columbia in Vancouver, Canada; and Roswell Park Cancer Institute in Buffalo, NY.

For this study, a total of 1,153 incident cases of invasive breast cancer were identified from CBCS, of which 61% were deemed to have adequate tumor and immunohistochemical surrogates (IHC) data for a subtype analysis. These cases included 196 African-American and 300 nonblack women. These cases were also more likely to be stage II and less likely to be stage I.

According to the results, IHC -- or genetic profile -- subtypes differed significantly by age, race, and menopausal status. The authors found that the prevalence of basal-like breast cancer was significantly higher in African-American breast cancer cases (26% versus 16% in nonblack women), and was seen mostly in premenopausal women (39%).

"The basal-like subtype has been associated with poor clinical outcomes, which likely reflect this subtype's high proliferative capacity," Carey's group explained.

Based on the CBCS follow-up of 11.2 years, the study patients had 73% overall survival. Of the 232 deaths, 80% were considered breast-cancer specific. African-American women had worse breast-cancer specific survival (74%) than nonblack women (84%), the group wrote.

"Basal tumors were more frequent in younger African-American women ... and could contribute to their poor prognosis compared with other breast cancer patients," the authors concluded. They also hypothesized that "the absence of BRCA1 carriers among African-American breast cancer patients in the CBCS suggests that genes other than BRCA1 could predispose women to basal-like breast cancers."

However, future studies should take into account the socioeconomic and environmental factors that may influence cancer risk in African-American women, the authors noted. Other areas that still need to be explored more fully are long-term survival of patients with specific breast cancer subtypes and therapeutic management of basal-like breast cancer in young African-America women.

By Shalmali Pal
AuntMinnie.com staff writer
June 6, 2006

Breast cancer deaths higher among black women, March 22, 2006

Cosmetic results good, toxicity mild with accelerated partial-breast irradiation, March 20, 2006

APBI variables affect late tissue toxicity, cosmetic outcome, February 13, 2006