Omission in Breast Cancer: When to Leave Radiation Behind and How to Mitigate Disparities

Reshma Jagsi, MD, DPhil

Better defining which groups of patients with breast cancer can safely omit radiation was at the forefront of research in 2023, with investigators becoming comfortable advising certain groups of patients now that more data has shed light on risks of recurrence, according to Reshma Jagsi, MD, DPhil. Investigators are also completing studies and designing interventions aimed at combating disparities within the profession of oncology, says Jagsi.

“The phase 2 PRIME II trial [ISRCTN95889329] is the best trial to point to because it was a randomized trial whose data showed there is a benefit from radiation treatment for pretty much any group of patients, even [those with] highly favorable select [characteristics]. But in some subgroups of patients, the risk of recurrence even without radiation is reasonably low enough that some women might want to choose to omit radiation,” Jagsi explained regarding key research published in 2023.

In PRIME II, 10-year outcomes were reported in patients 65 years or older with node-negative, hormone receptor (HR)–positive, T1 or T2 primary breast cancer who received breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. The study demonstrated that the cumulative incidence of local recurrence was 9.5% (95% CI, 6.8%-12.3%) for those who did not receive radiotherapy (n = 668) vs 0.9% (95% CI, 0.1%-1.7%) for patients who received radiotherapy (n = 658). However, 10-year overall survival rates were 80.8% (95% CI, 77.2%-84.3%) vs 80.7% (95% CI, 76.9%-84.3%), respectively.¹

Additionally, research published in 2023 revealed the positive impact of changes made during the COVID-19 pandemic to support faculty who are caregivers in medicine, providing a framework to guide sustainable change. Fifty-two medical schools and 2 research institutions applied to the COVID-19 Fund to Retain Clinical Scientists Program in 2021, in which the Doris Duke Charitable Foundation recognized medical schools during the pandemic. Support was given in the domains of regular and emergency dependent care, career and workplace flexibility, career development support, institutional culture change to reduce caregiver stigma, focused strategies to support women and underrepresented in medicine faculty career development support, and institutional culture change.²

In an interview with OncLive®, Jagsi, the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology at Emory University School of Medicine in Atlanta, Georgia, detailed the burgeoning advances from 2023 in breast cancer radiation oncology.

OncLive: What key changes to the breast cancer treatment landscape occurred in 2023 that impacted your practice or have the potential to impact it going forward?

Jagsi: There were several studies reported in 2023 that looked at de-escalation of radiation treatment, even looking at the opportunity to omit radiation treatment in patients with select favorable characteristics [such as] older women with early-stage HR-positive, node-negative disease after breast-conserving surgery. There were a couple of landmark papers published, including the PRIME II trial, LUMINA trial [NCT01791829], and my own study the IDEA trial which was presented at the San Antonio Breast Cancer Symposium 2023. These were studies that explored the omission of radiation treatment.

The flip side of this is that there have been many meaningful advances in radiation treatment delivery that the press sometimes got wrong with the headlines they ran with those studies when they came out. The media unfortunately overemphasized the toxicity and the burden of radiation treatment, which of course are meaningful and not equitably allocated across all patient groups— [the toxicities and burden] are worthy of us striving to avoid. That is why I’m one of the people who led 1 of those studies and why we try to investigate ways to omit radiation.

However, we have to be very careful when presenting these results to patients to make sure they understand both the risks and the benefits of radiation treatment. Radiation [oncology] is the only specialty that has a ‘danger: radiation’ sign that comes immediately to mind when you think about the treatment modality that we use. Patients are scared of radiation, and we don’t want patients who don’t fall into these favorable groups where there’s clearly a substantial benefit from radiation to be scared about radiation. Nor do we want patients who are in populations where there is some benefit from radiation treatment to dismiss that benefit without understanding the current experience of radiation treatment.

There were some other great advances in 2023, there was a new guideline published for accelerated partial breast irradiation that gave a comprehensive overview of the tremendous advances that we as a field have made in terms of identifying much more minimalistic treatments.

What were some highlights in breast cancer research in 2023 and how will they inform care and future studies?

In terms of treatment advances in radiation oncology, there have been several studies looking at omission of radiation treatment for older women with node-negative HR-positive breast cancer who received breast-conserving surgery. We now would feel pretty comfortable offering patients, if they’re 65 and older, the option of omitting radiation treatment but with the caveat that the risk of recurrence at 10 years is about 10% without radiation, and only 1% or 2% with radiation, even in that highly selected subgroup of patients.

Many patients can also avail themselves of the advances of ultrahypofractionated whole breast radiation, which has a somewhat shorter follow-up, as well as accelerated partial breast irradiation, which has good long-term follow-up. We can probably get the treatment done in 5 fractions [with either approach].

Given that, we have to be particularly cautious for patients where there might not be an intention to adhere to endocrine therapy or where there might be higher-grade disease that is very low in terms of receptor positivity. Low receptor positivity and the lack of persistence with endocrine therapy were pulled out as risk factors for recurrence in the PRIME II trial.

We’ve learned a lot about patient selection [and] how to administer treatment more efficiently with lower doses to normal tissues. That’s a key takeaway from this regional nodal irradiation meta-analysis—we have made truly meaningful advances, and we have seen the transformation of the most worrisome potential complications of radiation therapy as a result. 2023 was quite a year for radiation oncology and for breast cancer [with so many key analyses and trial data published].

Is there any ongoing research you’re participating in that you’d like to highlight?

We are trying to approach equity within the profession of oncology and medicine more generally with a lens towards being evidence based, as we are an evidence-based profession to begin with. We know that there are unacceptable inequities in advancement in our profession—we see women and people of color and other minoritized groups persistently underrepresented in the positions of greatest influence and authority in our field guiding the types of scientific questions we ask and doing the work that is important for our patients.

Unless our leadership in academic medicine reflects the diversity of the full talent pool that is available to it and the patient population we serve, we’re not going to fulfill our mission. We have several studies that are ongoing in that area, seeking to address the underlying drivers of those disparities within the profession, including differences in responsibilities for family caregiving and systems-level interventions to try to make sure that we support people with family caregiving responsibilities. Interventions to make sure that we are not engaging in gender bias or overt harassment or discrimination [are being created].

[Additionally], processes that are in place to make sure that we conduct our searches for positions and our processes for promotions as well as compensation [are being evaluated]—we are making sure they’re all criterion based, transparent, and consistent. We also have leadership development and career development interventions that we are evaluating in a randomized trial I recently completed of a leadership development intervention that is intended to help us transform the fates of the leaders of our profession for the benefit of our patients and our society.

References

1. Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388(7):585-594. doi:10.1056/NEJMoa2207586
2. Cutter CM, Szczygiel LA, Jones RD, Perry L, Mangurian C, Jagsi R. Strategies to support faculty caregivers at U.S. medical schools. Acad Med. 2023;98(10):1173-1184. doi:10.1097/ACM.0000000000005283