A new study provides evidence that older women with early-stage breast cancer who undergo radiation therapy following a lumpectomy are less likely to require a subsequent mastectomy.
A study published in Cancer, the journal of the American Cancer Society, provides evidence that older women with early-stage breast cancer who undergo radiation therapy following a lumpectomy are less likely to require a subsequent mastectomy. This is contrary to current recommendations that suggest radiation therapy does not play a role in determining whether an older woman will need a mastectomy following a lumpectomy for her early-stage breast cancer. The authors suggest the current recommendations are based on inaccurate thinking of the risks and benefits of radiation therapy.
Lumpectomy: The retracted pectoralis minor showing the axillary clearance of the level-III group of axillary lymph nodes. Source: Chintamani, Rohan Khandelwal, Megha Tandon, et al.
“Even among this highly-selected group of older patients with lower-risk early breast cancer, there is a measurable association between radiation therapy and lower risk of subsequent mastectomy,” said Jeffrey Albert, MD, of the M.D. Anderson Cancer Center in Texas and lead author of the Cancer paper. The study, however, is only a subset of older women with breast cancer, those aged 70 or older with small tumors, less than 2 cm, and node-negative, estrogen receptor–positive disease who have received endocrine therapy.
The authors have recently studied the wider population of older women with breast cancer and published a nomogram, or individualized risk predictor that facilitates outcomes predictions. The nomogram has been published in the Journal of Clinical Oncology. “We are currently developing an easy-to-use online version of this tool which we plan to make publicly available on the M.D. Anderson website,” said Albert.
The results suggest baseline characteristics that can identify those women who would most likely benefit from radiation therapy following lumpectomy and reducing unnecessary radiation therapy that adds cost and morbidity for patients. In a real-world setting, the study suggests radiation therapy after a lumpectomy is associated with a greater chance of avoiding a mastectomy for women ages 70 to 79 with early-stage breast cancer.
Benjamin Smith, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues used population-based data from the Surveillance, Epidemiology, and End Results–Medicare database to provide the risk of mastectomy for women 70 years and older and the benefit of radiation therapy to outcomes. The study cohort consisted of 7,403 women between the age of 70 and 79 who were diagnosed between 1992 and 2002. About 88% of the women in the cohort received radiation after their lumpectomy.
The current national guidelines suggest women older than 70 with early-stage breast cancer that has not yet spread to the lymph nodes and is driver by estrogen can be treated well with a lumpectomy and estrogen inhibitor without radiation therapy. Because older women have a lower risk for recurrence, the outcome of omitting radiation therapy from the treatment regimen has been addressed in several trials including the Cancer and Leukemia Group B (CALGB) 9343 trial, that included women aged 70 years and older with stage I, estrogen receptor (ER)–positive breast cancer. All of the women were randomized to either radiation therapy or no radiation therapy following a lumpectomy and tamoxifen treatment. At a 10-year follow-up, the results showed radiation therapy did lower the risk of local recurrence, but the risk reduction was not statistically significant.
“The major influential CALGB 9343 study showed a modest benefit in local control with radiation but no improvement in mastectomy-free survival,” explained Albert. “Based on these data, the National Comprehensive Cancer Network (NCCN) guidelines now state that it is appropriate to omit radiation for this group of patients.” Because breast preservation is the primary goal of radiation therapy for older patients, the authors wanted to look at the association of radiation therapy and the risk of needing a subsequent mastectomy for patients treated in a real-world setting, not in a highly-controlled clinical trial setting.
Treatment with radiation therapy was associated with a lower risk of a subsequent mastectomy. The 10-year risk of a mastectomy was 6.3% in patients who did not receive radiation therapy compared to 3.2% of those who did (P < .001). The risk was lower for women of all ages and grades of breast cancer. The median patient follow-up of the population cohort was 7.3 years with complete follow -up of 10 years available for 50% of patients. Within 9 months of the initial diagnosis, 174 patients (2.4%) had a mastectomy.
Type of lymph node assessment was significant in terms of mastectomy risk. Radiation therapy was associated with a greater reduction in mastectomy for patients who had clinically assessed lymph node status (P < .001) compared to those who had pathologically assessed lymph node status (P = .015). The absolute risk reduction was 4.9% for those women who had clinically assessed lymph nodes and had radiation therapy compared to those who did not under radiation.
The study also identified that women between the ages of 75 and 79 with non–high-grade tumors who underwent pathologic axillary nodal assessment had no benefit from radiation therapy. This result is consistent with that of the CALGB 9343 randomized study. In contrast, women with high-grade breast cancer had a 6.7% absolute reduction in 10-year risk of mastectomy.
“Findings from our analyses support our hypothesis that the risk of subsequent mastectomy and the absolute reduction in risk conferred by radiation therapy appear slightly greater in routine practice than in the clinical trial setting,” conclude the authors.
Caveats to the study include a lack of information on the reason for mastectomy and retrospective data analysis. Furthermore, there is no data on endocrine therapy which is known to lower the risk of recurrence.
Albert adds that while this was not a prospective, randomized controlled trial, guidelines that capture many factors based on retrospective, carefully analyzed studies can greatly facilitate individualized decision-making for cancer patients. “Since many clinical trials do not enroll enough patients to have sufficient statistical power to analyze subgroups, we believe that data from studies such as ours can help augment the data available from clinical trials to inform individualized decision-making between patients and physicians,” Albert said.