Breast Cancer Research Begins With Curiosity

Getting a start in clinical research can appear daunting, said Anees Chagpar, MD, MBA, MPH, FACS, FRCS(C). Fortunately, all it really takes is a question and a bit of drive.

“For people who may be intimidated by clinical research, know that there’s a lot of meaningful questions that you can ask. If you have a question about [something]—maybe it’s a question that came up in your tumor board or something that you’ve been wondering about—oftentimes, those are great questions to answer,” said Chagpar, a professor in the Department of Surgery at Yale School of Medicine in New Haven, Connecticut. “If you have that question, it’s likely that other people do, too. You can either dive right in and answer that question or get a mentor to help you through the process.”

Chagpar, a cochair of the 39th Annual Miami Breast Cancer Conference^® (MBCC), is slated to deliver a presentation on breaking into clinical research and recognizing research ideas worth pursuing today. Conference organizers have long emphasized that the MBCC audience extends beyond established investigators to include junior faculty, clinicians, and supportive care specialists, among others. Chagpar noted that her presentation is aimed at those who are interested, but inexperienced, in research.

“One of the things that’s great about the Miami Breast Cancer Conference^® is that it really brings together all kinds of people in the community who are dedicated to delivering the best quality of care to patients with diseases of the breast,” she said. “Yes, it does bring together some of the biggest national experts who are very well versed in clinical research, but it also brings together some of those frontline [individuals]—[those] who are in the trenches, delivering care to [patients] with breast cancer every day—who may or may not be as involved in clinical research, but who may really be interested in how they can really contribute [and] how they can move the field forward.”

Chagpar is a passionate advocate for research because she believes it is the only way to move the field forward, she said. Without the intellectual humility to ask the questions, medical science will be stuck in the status quo. “That simply isn’t good enough,” she added. “It’s not good enough for us as clinicians, and it’s not good enough for our patients.”

Research Worth Pursing

The other half of Chagpar’s presentation will focus on helping her audience recognize a worthwhile research question. Although she says that “almost all research” has value, she hopes to help those who might be intimidated about getting involved in research break through their fear.

A research question is likely to have value because there is a good chance that other people may have the same question, Chagpar said. Even in the event the question has been addressed in a trial, it is still possible to explore data in other patient populations or to analyze that data from a different angle. Trials that validate or contradict earlier findings have value as well.

Worthwhile research, she said, begins with an interesting question that is then evaluated with an appropriately designed study. Finally, the results need to expand the field of knowledge and/or change practice.

“If you can see your way to a question that you think would [address an important concern], whether it’s a question that you’ve just been wondering about, or perhaps something that came up at your tumor board, then that’s a valid question,” she said. “And you should pursue it.”

Chagpar pointed to a trial investigating cavity shave margins in breast cancer (NCT01452399) that grew out of her own curiosity after listening to a presentation from UT Southwestern Medical Center that described a different method for performing a lumpectomy. Surgeons had long debated how to reduce positive margin rates. Although many x-rayed the specimen and took extra tissue only if the tumor abutted an edge, others advocated removing circumferential cavity shave margins (CSM) regardless of the x-ray.

Those opposed to the latter technique argued that it unnecessarily removed more tissue and could affect the cosmetic outcome. However, in their retrospective study, the team at UT Southwestern found that patients who underwent CSM were less likely to require further resection compared with those who had conventional surgery (21.7% vs 42.0%).¹ Furthermore, CSM excised less tissue than standard therapy (80.7 cm³ vs 165.1 cm³) while improving cosmesis.²

Chagpar said the results confused her because it’s not possible to take more tissue but end up taking less tissue.

“There’s only 1 possible explanation...as to how that could be the case. And that is that the surgeons who knew that they were going to take more all the way around...took less to begin with,” she said. “So then when they took more, it ended up being the same amount of tissue as the [surgeons] who took a bigger piece to begin with—they knew that they weren’t going to take more.”

Her desire to rectify that mathematical impossibility led to the SHAVE trial (NCT01452399), a prospective, randomized, controlled trial to evaluate routine excision of CSM as a technique for reducing the rates of positive margins and re-excision. In findings published in the New England Journal of Medicine in 2015, patients randomly assigned to the CSM group had a significantly lower rate of re-excision than those assigned to the no-shave group (10.0% vs. 21.0%, P = .02). Although those assigned to CSM did have more tissue removed, there was no significant difference between the 2 groups in the patients’ perception of their cosmetic outcomes (P = .69).³

“We found that by taking tissue all the way around, [we] actually reduced the positive margin rate and the re-excision rate by 50%,” Chagpar aid. “And yes, there was a difference in the volume of tissue removed, as you would expect, but it did not affect the cosmetic outcome.”

Results from multicenter trials have since validated those findings. Chagpar’s imagination, inspired by observations from UT Southwestern, led to changes in clinical practice.

“How did that happen? It happened just out of curiosity,” she said. “When I mentor students and residents and fellows, I always tell them to unlock their inner 2-year-old. Figure out what you’re really curious about…what you’re passionate about. That’s where the best questions come from.”

References

1. Kobbermann A, Unzeitig A, Xie XJ, et al. Impact of routine cavity shave margins on breast cancer re-excision rates. Ann Surg Oncol. 2011;18(5):1349-1355. doi:10.1245/s10434-010-1420-6
2. Mook J, Klein R, Kobbermann A, et al. Volume of excision and cosmesis with routine cavity shave margins technique. Ann Surg Oncol. 2012;19(3):886-891. doi:10.1245/s10434-011-1982-y
3. Chagpar AB, Killelea BK, Tsangaris TN, et al. A randomized, controlled trial of cavity shave margins in breast cancer. N Engl J Med. 2015;373(6):503-510. doi:10.1056/NEJMoa1504473