Per Karlsson, MD, PhD: New Data on Breast-Conserving Surgery, With or Without Radiotherapy
2022 San Antonio Breast Cancer Symposium
Per Karlsson, MD, PhD, of Sweden’s University of Gothenburg and the Sahlgrenska Comprehensive Cancer Center, discusses results from the POLAR study, which was a meta-analysis of three clinical trials of breast-conserving surgery with or without radiotherapy. POLAR is the first genomic classifier that appears not only to be prognostic for locoregional recurrence, but also predictive of radiotherapy benefit. Although patients with breast cancer who had a high POLAR score benefited from radiotherapy, patients with a low score did not, and may be candidates for omission of radiotherapy after breast-conserving surgery (Abstract GS4-03).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
We have performed a patient level meta-analysis and we have included three different studies, studies randomizing patients to radiotherapy or no radiotherapy. The studies included were the Swede BCD 921 study, the Princess Margaret study, and the Scottish Conservation RT Trial. The patient level meta-analysis has the objective to analyze the performance of the POLAR signature as a prognosticator for locoregional recurrences in the new RT arm and also as a potential predictive assay for radiotherapy benefit.
It's well known that radiotherapy reduces the risk for locoregional recurrences in all different clinical subgroups today. There are definitely some need to find new classifiers to understand which patient we can omit the radiotherapy for.
We have within the Swedish trial identified a signature for RT remission, but that signature must be validated in further studies. Now we have performed this patient-level meta-analysis, but to send some word about the development of the signature in the Swedish study, we have collected all the blocks from the tumors and we have punched the tissues and isolated RNA, and this RNA has given us gene expression info. We have used array-based methods for that.
Using this information, we have filtered the genes most prognostic for locoregional recurrences in the new RT arm. We have further [inaudible 00:01:52] the genes at the enrichment analysis. This filtering has resulted in genes that were fed into a regression model. This regression model resulted in the POLAR score.
The POLAR score consists of 16 genes. The gene functions here is about immune response and also about proliferation. Now we have used this POLAR score and applied that in this patient meta-analysis, and we could see that POLAR could prognosticate the locoregional recurrence in all the new RT arm in all these three different studies. We also find that the POLAR RT had a significant interaction, which means that this classifier is a predictive for radiotherapy benefit. But all this has been done retrospectively. So going further to use it in clinical practice, I think we need further validation, but this is, to our knowledge, the first genomic classifier that can predict radiotherapy benefit. So hopefully in the future we can use this assay to know which patient we can omit radiation. So that's the way forward for us.
Judy C. Boughey, MD, of Mayo Clinic, talks about why breast-conserving therapy may be a treatment option for some patients with multiple breast lesions. For most patients who present with two or three sites of cancer in one breast, mastectomy is recommended. But results from the ACOSOG Z11102 (Alliance) suggest that for women with multiple ipsilateral breast cancer, breast-conserving surgery with adjuvant radiation therapy and lumpectomy site boosts may be beneficial (Abstract GS4-01).
Sean Khozin, MD, MPH, of the Massachusetts Institute of Technology, discusses the “external validity deficits” of randomized clinical trials, which still involve only about 5% of adults with cancer, who may differ in important ways from real-world populations. Dr. Khozin describes the reasons for low levels of participation and advocates for capturing the experience of patients not represented in traditional clinical trials, so real-world data can address these validity deficits.
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, discusses results from the POSITIVE trial, which showed that a temporary interruption of endocrine therapy in women with hormone-responsive breast cancer in order to attempt pregnancy, does not affect short-term disease outcomes. The study found that 74% of women had at least one pregnancy, most (70%) within 2 years. Birth defects were low (2%) and were not clearly associated with treatment exposure. Dr. Partridge explains that these data stress the need to incorporate patient-centered reproductive health care in the treatment and follow-up of young women with breast cancer (Abstract GS4-09).
Aditya Bardia, MD, MPH, of Massachusetts General Hospital, discusses results from the phase III EMERALD trial, the first study to demonstrate improved progression-free survival vs standard of care in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer with one to two prior lines of endocrine treatment, with or without one line of chemotherapy. This finding applied to all patients in the study, including the subgroup with ESR1 mutations (Abstract GS3-01).
Joseph A. Sparano, MD, of the Tisch Cancer Center at Mount Sinai Health System, discusses long-term clinical outcomes data that continue to show many women with early breast cancer can safely forgo chemotherapy, when guided by the 21-gene recurrence score result. The longer follow-up also showed that recurrences of breast cancer continue to occur years after the original diagnosis, although these recurrences were not prevented by chemotherapy use. Racial disparities were not explained by inequities in social determinants of health or treatment adherence, with Black women at higher risk of early recurrence within the first 5 years of diagnosis, but not later recurrence after 5 years (Abstract GS1-05).