Brachytherapy Reduces Breast Cancer Recurrence in Tumor Bed

Nancy A. Melville

May 04, 2012

May 4, 2012 (Phoenix, Arizona) — Accelerated partial-breast irradiation (APBI), or brachytherapy, is more effective than whole-breast irradiation (WBI) at preventing breast cancer recurrence after lumpectomy, according to research presented here at the American Society of Breast Surgeons 13th Annual Meeting.

Lumpectomy with WBI is associated with a rate of survival no worse than with mastectomy; however, the therapy has not been shown to affect "elsewhere" cancers that are not in the primary tumor quadrant.

Recurrence rates with WBI are known to be higher in the tumor bed than in ipsilateral elsewhere areas. A new study suggests that the focused APBI technology offers better control of tumor-bed breast cancer recurrence.

Dr. Peter Beitsch

Although it is common sense that "APBI offers better rates of local control than WBI, since the radiation therapy with APBI is delivered directly to the tumor site, this is the first study to have actually proven this hypothesis," lead author Peter Beitsch, MD, a surgical oncologist at the Dallas Surgical Group in Texas, told Medscape Medical News.

"WBI has been held as the gold standard for postlumpectomy radiation therapy. Our data may change that line of thought," said Dr. Beitsch.

Dr. Beitsch and his colleagues evaluated 1444 patients with early-stage breast cancer who had been treated with APBI after lumpectomy.

They found that, after a mean follow-up of 60 months, there were 50 cases (3.5%) of ipsilateral breast tumor recurrences among patients treated with APBI (34 Gy in 3.4 Gy fractions). The 5-year actuarial rate for ipsilateral recurrences was 3.61% (3.65% for invasive breast cancer and 3.36% for ductal carcinoma in situ [DCIS]).

Just 14 of the ipsilateral breast tumor recurrences (1.0%) were associated with tumor-bed failures, compared with 36 (2.5%) elsewhere failures (72% of all ipsilateral recurrences).

There were 1255 (87%) patients with invasive breast cancer (median size, 10 mm) and 194 (13%) with DCIS (median size, 8 mm).

The only variable associated with ipsilateral breast tumor recurrences was estrogen-receptor negativity (= .0004).

In the DCIS group, however, age younger than 50 (= .0431) and close/positive margins (P = .0551) were associated with increased ipsilateral recurrences.

Dr. Beitsch explained that results are likely explained by the precision of APBI in targeting the site of the original tumor, which is the site most at risk for tumor recurrence.

"The 'bioequivalent' dose of radiation therapy to the breast is similar between APBI and WBI, but the radiation therapy is not 'diluted' by applying it to the entire breast," he said.

"The targeted radiation is delivered from within the lumpectomy bed to the cavity walls. The entire reason for radiation after lumpectomy for early-stage breast cancer is to kill the residual cancer cells," he explained.

He described WBI as "a cannon" and APBI as a "sniper rifle."

"APBI therapy targets the tissue at risk and avoids normal tissue — ribs, lung, heart, pectoralis muscle."

A larger study of nearly 93,000 women (JAMA. 2012;307:1827-1837) had contradictory findings. It found APBI to be associated with a higher risk for infection and complications and a lower risk for long-term breast preservation in older women with invasive breast cancer, compared with WBI.

In contrast to the study by Dr. Beitsch and colleagues, which involved a registry in which patients were treated and reported in "real time, the JAMA study was a retrospective review of a Medicare billing claims database.

"One of the main conclusions of the [JAMA] study is that patients undergoing APBI subsequently had a mastectomy at twice the rate of patients undergoing WBI," Dr. Beitsch explained.

"However, it is impossible from a claims database to know why those patients underwent mastectomy. Was it due to a local recurrence, a new cancer somewhere else in the breast, even a new cancer in the other breast? Neither 'elsewhere' failures nor new breast cancers in the other breast are prevented by WBI," he explained.

Dr. Beitsch added that the study lacked clinical data on where in the body the increased infections were, and it fails to address the death rate associated with WBI.

"There was actually a higher death rate with WBI that was dismissed on multivariate analysis, which mastectomy rate was not subjected to," he said. "I find this interesting in light of the pejorative way APBI is described as 'harming patients.' Isn't the worst possible harm death?"

Dr.Benjamin Smith

Benjamin Smith, MD, lead author of the JAMA study, agrees that the claims data were a limitation of his study; however, he noted that the study has strengths that help address limitations in the study by Dr. Beitsch's team.

"It is an important limitation of the JAMA study that the indication for mastectomy cannot be definitely determined from claims, although mastectomy in and of itself is obviously a clinically relevant outcome," said Dr. Smith, assistant professor in the Department of Radiation Oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Beitsch and colleagues do not have data on "the treatment of in-breast tumor recurrence for 24% of the recurrences [12 of 50 cases]. Our data can provide a nice complement to their data, since we have complete data on subsequent surgeries performed on patients after treatment with brachytherapy," Dr. Smith told Medscape Medical News.

He suggested that various factors could explain why there were proportionally fewer tumor-bed recurrences with brachytherapy than elsewhere recurrences in the study by Dr. Beitsch's team.

"If it is true that the proportion of tumor-bed recurrences to elsewhere recurrences is lower for patients treated with brachytherapy than with whole-breast irradiation, this could be due to either a lower risk of tumor-bed recurrences in patients treated with brachytherapy or, conversely, a higher risk of elsewhere recurrences," Dr. Smith said.

"It is almost certain that patients treated with brachytherapy will have a higher risk of elsewhere tumor recurrences, as 'elsewhere' is not irradiated," he explained.

"It is probably more important to evaluate absolute risks of tumor-bed recurrences and elsewhere recurrences in matched patients treated with brachytherapy or whole-breast irradiation, instead of comparing the proportion of these 2 events."

Dr. Beitsch has disclosed no relevant financial relationships. Dr. Smith reports receiving research funding from Varian Medical Systems, which makes radiation equipment for both whole-breast irradiation and brachytherapy; however, the research funding was not used for any portion of this study.

American Society of Breast Surgeons (ASBS) 13th Annual Meeting: Abstract 0058. Presented May 4, 2012.

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