SABCS 2022: When Treating Breast Cancer, Less May Be More 

Cancer treatment is a double-edged sword. Intense or multi-pronged treatment may lead to better killing of tumor cells, but it can often cause debilitating side effects.   

Is it possible to reduce the intensity of cancer treatment, and potentially improve quality of life, without adversely impacting clinical outcomes? 

The answer might be yes, according to two studies presented December 9 at the San Antonio Breast Cancer Symposium, which is co-sponsored by the AACR.  

Both studies evaluated the impact of less intensive treatment on the risk of local recurrence in patients with breast cancer. We summarize the major findings below. 

More patients could opt for breast-conserving therapy 

Some patients with breast cancer who undergo surgery have the choice between a mastectomy, which removes the entire affected breast, or the less invasive option of a lumpectomy followed by radiation therapy. 

“Lumpectomy with radiation therapy is often preferred to mastectomy as it is a smaller operation with quicker recovery, resulting in better patient satisfaction and cosmetic outcomes,” said Judy Boughey, MD, the presenter of one of the studies. 

Unfortunately, patients who have multiple tumors in the same breast, known as multiple ipsilateral breast cancer, may not have this option.  

“Historically, retrospective studies have shown high rates of local recurrence in patients with multiple ipsilateral breast cancer, and this leads many surgeons to recommend mastectomy to this patient cohort,” Boughey said. However, modern advances in imaging and radiation therapy may lessen the risk of recurrence after breast-conserving therapy, an idea supported by more recent retrospective studies. 

To examine whether breast-conserving therapy could be a viable option for these patients, Boughey and colleagues conducted a prospective single-arm phase II clinical trial, Z11102, in which patients with two or three sites of breast cancer in the same breast underwent breast-conserving therapy. This is the first prospective clinical trial to investigate this question, Boughey said. 

Among the 204 evaluable patients, only six patients experienced a local recurrence, for a five-year local recurrence rate of 3.1 percent. This rate was similar to the local recurrence rates seen in prior studies for patients with a single breast tumor who underwent breast-conserving therapy, Boughey noted. 

Local recurrence was more common among patients who did not undergo a pre-surgical breast MRI compared with those who did (22.6 percent vs. 1.7 percent). Boughey theorized that breast MRI may have provided greater detection of disease sites prior to surgery, potentially allowing for more thorough resection. Based on these results, she suggested that patients who are considering breast-conserving therapy may benefit from pre-surgical breast MRI. 

This study provides important information for clinicians to discuss with their patients who have several foci of breast cancer in one breast, Boughey concluded. “It is exciting to see that breast-conserving therapy is a reasonable consideration in multiple ipsilateral breast cancer.” 

Identifying patients who can skip radiation after a lumpectomy 

Current clinical practice dictates that patients who opt for a lumpectomy should receive subsequent radiation therapy to reduce their risk of recurrence; however, data from a study presented at SABCS suggests that some patients can safely skip radiation, and a new genetic signature may help identify who those patients are. 

“Many patients will not experience a local recurrence even without radiation therapy,” said Per Karlsson, MD, a professor of oncology at the Sahlgrenska Comprehensive Cancer Center and the University of Gothenburg in Sweden, who presented the new data.  

“Since radiation therapy can be associated with problematic side effects in some patients, it is of clinical importance to identify those patients for whom radiation therapy can be safely omitted,” Karlsson said. Currently, there are no reliable methods to predict which patients might be able to skip radiation therapy. 

In this study, Karlsson and colleagues evaluated the predictive potential of POLAR (Profile for the Omission of Local Adjuvant Radiotherapy), an investigational 16-gene molecular signature that was developed based on gene expression differences between patients with and without local recurrence after breast-conserving surgery. None of the 16 genes included in POLAR are found in Oncotype DX, a predictive tool used to predict recurrence in patients with breast cancer.  

The researchers performed a meta-analysis of 623 patients with lymph node-negative, estrogen receptor-positive, HER2-negative breast cancer who were enrolled in one of three randomized clinical trials examining the efficacy of lumpectomy with and without local breast radiation therapy. The clinical trials included in the meta-analysis were the Swedish SweBCG91RT trial, the Scottish Conservation Trial (SCT), and a trial from the Princess Margaret Hospital (PMH) in Canada.  

To evaluate the predictive capability of POLAR, the researchers analyzed gene expression in patient breast tumor samples to assign each patient a POLAR score; they then examined the impact of radiation therapy for patients with high and low POLAR scores.  

Among patients with low POLAR scores, there was no significant difference in local recurrence rate between those who received adjuvant radiation therapy and those who did not. In contrast, radiation therapy significantly reduced the risk of local recurrence in patients with high POLAR scores. 

“While patients with a high POLAR score benefit from radiotherapy, patients with a low score do not benefit from radiotherapy and may, therefore, be candidates for omission of radiotherapy after breast-conserving surgery,” summarized Karlsson, noting that further study in contemporary trials is needed. 

“Although only a minority of patients experience severe side effects to breast radiation, this adds up to a fair number of patients once you consider how prevalent breast cancer is,” he added. “The POLAR gene profile may, therefore, help mitigate toxicities and improve quality of life for many patients.”