When less is more in breast cancer treatment

Recent studies have suggested that standard treatments such as chemotherapy, radiation and surgery, particularly mastectomy, that are recommended for early stage breast cancer may not always be needed for precancerous lesions, such as ductal carcinoma in situ (DCIS). These treatments may expose women with DCIS to unnecessary adverse effects without added benefit. There is disagreement in the oncology community whether DCIS should be treated like early stage breast cancer or if a “watch and wait” strategy may be more appropriate for, or even desired, by some patients. 

BCRF investigator Dr. Fatima Cardoso chaired an education session to discuss the latest evidence on overtreatment and the appropriate use of available therapies. In her presentation, Dr. Cardoso discussed the use of gene signatures for a more individualized approach. For some patients, she said, chemotherapy is still the best approach and is “indispensable for achieving cure.” The challenge is in identifying which women need chemotherapy and which do not. New gene-based diagnostic tests such as Oncotype DX® and the MammaPrint® have been shown to help in this regard.  Dr. Cardoso discussed the recent results from the MINDACT trial that demonstrated that the MammaPrint 70 gene recurrence score was better than clinical assessment of tumors in predicting which women were at low-risk of recurrence and thus could forego chemotherapy after surgery (known as adjuvant therapy). Similar results from the TAILORx study reported that the Oncotype DX® recurrence score could help identify women with early stage, estrogen receptor-positive breast cancer who could forgo chemotherapy.

In the same session, BCRF investigator, Dr. Laura Esserman presented a case that indolent or “ultra-low” risk cancers now comprise up to 30 percent of screening-detected breast cancers. She presented data based on studies with more than 20 years of follow up supporting a “less is more” approach to some DCIS. The major challenge remains in being able to identify which DCIS are “ultra-low” risk from those that are high-risk and should be treated. She referred to soon-to-be published work from her group validating a MammaPrint®- derived ultra-low risk predictive score in a large cohort of Swedish women. She also recommended adapting a personalized approach to screening based on risk as opposed to age and pointed to the WISDOM trial (Women Informed to Screen Depending on Risk) as an effort to learn from risk-based screening in order to improve screening strategies. 

Dr. Shelley Hwang (Duke University) ended the session with a discussion on how to balance the risks of treatment options (systemic therapy, surgery and radiation) with benefits for patients with low grade DCIS. She emphasized the need for precision medicine for low-risk DCIS that balances the risk of morbidities associated with treatment and accepts some degree of uncertainty of outcomes.  Dr. Hwang described the COMET trial (Comparison of Operative vs. Medical Endocrine Therapy for low-riskDCIS) which plans to recruit about 1,200 women who will be randomized to receive usual care or receive active surveillance. The trial seeks to reduce the uncertainty of outcomes for either method and will compare clinical outcomes as well as patient reported outcomes, such as psychosocial stress. The study has the potential to guide care choices for early stage breast cancers and potentially help women avoid the adverse effects of treatments that would provide no benefit. 

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