Research looks to avoid overtreatment in early-stage breast cancer

Background

Many hormone receptor-positive, HER2-negative breast cancers can be treated successfully with current standard treatments. Yet, today it is not straightforward for doctors to predict which of these cancers are at highest risk for recurrence. As a result, some people get more treatments than they may need to prevent cancer from coming back.

Breast radiation therapy can be very effective at preventing locoregional recurrence of early-stage breast cancer, when cancer returns to the same area of the breast or nearby lymph nodes. But it also extends a person’s time in treatment, requires many doctor’s visits and expenses, and can leave people grappling with fatigue, skin, and other side effects.

The Profile for the Omission of Adjuvant Radiation (POLAR) signature is a new tumor biomarker or genomic test that groups genetic characteristics found in some breast cancers. This test looks at 16 genes in what is called the POLAR signature. They are lesser-known genes that affect the body’s immune response or cell growth. The POLAR signature is distinct from the better known Oncotype Dx test, a tumor biomarker test that predicts the benefit of chemotherapy to reduce recurrence in some HR+ early breast cancers. POLAR is specifically linked to breast radiation therapy.

Results

This study is a pooled meta-analysis that summarizes the results of three randomized trials. It looks at whether the POLAR signature could in the future be used to help guide radiation treatment for people with early-stage breast cancer who can have lumpectomy surgery.

Tumor tissue from 623 people with early-stage, estrogen receptor-positive, HER2-negative breast cancer provided the sample for this study. The participants had a variety of other full-body treatments, with some receiving chemotherapy and some not, and all taking some type of hormonal therapy. The racial and ethnic makeup of the participants was not reported. Researchers looked at 10-year outcomes for those who went on to have a locoregional recurrence and those who did not. Participants were identified as either POLAR-high or POLAR-low, based on genomic testing.

The results were consistent across all three clinical trials. Breast cancer radiation therapy benefited those with high POLAR scores and was of little benefit to people in the POLAR-low group. Among the findings:

• The percentage of people in the POLAR-low group who had a locoregional recurrence was roughly the same for those who had radiation therapy and those who didn’t. This suggests those who got radiation therapy could have avoided it without increased risk for recurrence.
• Among people with POLAR-high cancers, 7% of those treated with radiation therapy had a locoregional recurrence at 10 years, compared with 20% of those not treated with radiation therapy. This suggests radiation therapy was effective in helping prevent recurrence in POLAR-high cancers.

While these results are very encouraging, they are drawn from a retrospective (or past) sample of prior testing and outcomes. They need to be tested in an active clinical trial.

What this means for you

The results of this study provide an important piece of information that will help doctors design research that may influence whether people with certain types of early-stage breast cancer will need radiation therapy in the future. Talk with your doctor about these results. This conversation could be part of a broader discussion about the goals of your treatment, taking part in a clinical trial, and the risks and benefits of each type of treatment you are considering.

POLAR testing may not be available at every hospital and cancer center. If your hospital does not offer this kind of testing, ask your doctor about having it done at a National Cancer Institute-funded cancer center or university health system. They may be able to send your sample for testing.

Other studies focusing on overtreatment

Eliminating overtreatment is a high priority research area in all stages of breast cancer. Other results also presented on December 9 at the 2022 San Antonio Breast Cancer Symposium addressed:

Removing fewer lymph nodes

New results support the use of sentinel lymph node biopsy (SNLB) with dual-tracer mapping or targeted axillary dissection (TAD) for people whose lymph nodes change from testing positive for cancer to negative after receiving pre-surgery, or neoadjuvant, chemotherapy.

The study presented reconfirms the safety of omitting traditional axillary lymph node dissection, an approach that removes more lymph nodes and carries more possible side effects. It found no difference in rate of recurrence at three years between the people who had SLNB with dual mapping and those who had TAD, but longer-term follow-up is needed to know whether the TAD technology can be safely used for this purpose. TAD is a newer approach that results in removing even fewer lymph nodes than traditional SLNB. It was developed to address the high rate of false-negatives in SLNB. The international participants in this trial included people with HER2- positive and triple-negative breast cancers, as well as those with hormone receptor- positive breast cancers.

Lumpectomy for cancer in multiple areas of the breast

Lumpectomy might be an option for people who have two to three lesions in a breast, according to study results presented at SABCS. At five years, 3.1% of participants experienced a local or nearby recurrence. This study included mostly postmenopausal women with hormone receptor-positive breast cancer who had two lesions in the breast and whose lymph nodes tested negative for cancer. More research is needed to confirm the safety of the finding.