Expert Picks Top Breast Cancer Papers of Last Year

LAS VEGAS—Nearly every year since 2003, Helen Pass, MD, has combed the literature to find what she considers the best of the previous year’s clinical papers on breast cancer to present at the annual meeting of the American Society of Breast Surgeons. By one estimate, she’s put at least 2,300 hours into this labor of love.

For 2024, she had more than 28,000 papers from which to select “the things you need to know Monday or to interact with your multidisciplinary team,” said Dr. Pass, the chief of breast surgery at NYU Grossman Long Island School of Medicine, in Mineola, New York.

Kerlikowske K, et al. Supplemental magnetic resonance imaging plus mammography compared with magnetic resonance imaging or mammography by extent of breast density. J Natl Cancer Inst. 2024;116(2):249-257.

In this retrospective review conducted between 2005 and 2019, researchers evaluated 52,237 women who underwent screening mammography alone or mammography plus MRI. The addition of MRI increased the detection of early-stage cancer and increased false positives, but did not decrease the rate of interval and advanced cancers. The authors concluded that enhanced screening for average-risk women with dense breasts may not be beneficial.

“We all get those mammogram reports that say in women who have dense breasts, we should consider supplemental screening. Do we? I think for women with no other risk factors we really may not need to do that.”

(All quoted comments in the article are by Helen Pass, MD.)

Metcalfe K, et al. Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis. Br J Cancer. 2024;130(2):269-274.

In this international study, women with BRCA1/BRCA2 mutations underwent either risk-reducing mastectomy (RRM) or active surveillance (827 participants in each arm). At 6.3 years’ follow-up, there were 20 incident cancers (15 of which were occult cancers found at the time of RRM), two breast cancer deaths in the RRM cohort, and 100 incident cancers and seven breast cancer deaths in the surveillance arm.

“RRM really does decrease the incidence of breast cancer, and we can get the probability of death very low. But patients are very specific about their preferences—internationally only about 30% of women choose RRM; the rest choose enhanced surveillance. I never tell a BRCA carrier that she has to have a bilateral mastectomy, whether she’s newly diagnosed with breast cancer or newly diagnosed with a deleterious mutation. I do counsel them about their options.”

Hwang ES, et al. Active monitoring with or without endocrine therapy for low-risk ductal carcinoma in situ: the COMET randomized clinical trial. JAMA. 2025;333(11):972-980.

The COMET trial, designed to compare invasive cancer rates in 957 patients with hormone receptor–positive, low-grade ductal carcinoma in situ (DCIS) randomized to either active surveillance or surgery, found no higher rate of invasive cancer at two years in the surveillance group. Of note, 44% of those randomized to surgery chose only surveillance, 11% of those randomized to surveillance underwent surgery, and 70% in both arms opted for additional endocrine therapy.

“We do need to recognize limitations: the crossover rate, the short follow-up. Nonetheless, for women with DCIS and a limited life expectancy, we can avoid surgery. For women who really want to avoid surgery, we can consider their preferences with appropriate counseling. But we know the upgrade rate at surgery is not trivial, and that if DCIS progresses to invasive cancer some women will die of their disease.

Dr. Pass recommended two editorials for further reading and more information (Morrow M, et al. JAMA 2025;333[11]:946-947; Khan SA, et al. JAMA 2025;333[11]:948-949).

Reimer T, et al. Axillary surgery in breast cancer—primary results of the INSEMA trial. N Engl J Med. 2025;392(11):1051-1064.

The INSEMA trial randomized 5,502 patients, most of whom had estrogen receptor (ER)-positive/HER2-negative, T1, grade 1 or 2 tumors, to either sentinel lymph node biopsy (SLNBx) or no axillary surgery. At 74 months, there was no significant difference in invasive disease–free survival, distant disease–free survival, or overall survival.

“This adds to the SOUND trial information, that select patients can avoid SLNBx. But questions remain about age, the inverse relationship between tumor size and grade, and whether or not a negative preoperative axillary sonography is required. Remember, if more advanced disease is discovered, you can consider a delayed SLNBx.”

Chun JW, et al. Oncological safety of skipping axillary lymph node dissection (SLND) in patients with clinical N0, sentinel node-positive breast cancer undergoing total mastectomy. Ann Surg Oncol. 2024;31(5):3168-3176.

This was a retrospective review of 643 women with up to two positive sentinel lymph nodes who underwent mastectomy, comparing oncologic outcomes between those who underwent SLND and those who had completion axillary lymph node dissection (cALND). Five-year disease-free survival and local recurrence-free survival were similar between the two groups; the addition of radiation therapy improved local regional relapse-free survival.

“This shows that the Z0011 criteria,” which compared SLND and cALND in women undergoing lumpectomy, “can be applied to women having a mastectomy. The AMAROS trial did include 18% of patients who underwent mastectomy with SLNBx and had up to three nodes positive, but that subset was very small, so this study it really adds to the data. As always, multidisciplinary discussion is critical.”

Maramara T, et al. Adherence rate to alliance for clinical trials in oncology Z0011 trial based on breast cancer subtype. J Am Coll Surg. 2024;238(4):656-667.

To evaluate the adherence rate to Z11 based on tumor subtypes, researchers queried the National Cancer Database (NCDB) on 33,859 patients meeting the Z11 criteria, classified into ER-positive/HER2-negative, ER-negative/HER2-negative, and HER2-positive. They concluded that Z11 applies regardless of subtype to women who meet the Z11 criteria, but that half of the patients are still undergoing cALND.

“People keep finding reasons that a patient doesn’t meet Z11 criteria, because in that study 70% of patients were ER-positive. In this study, there was no difference based on the patient’s subtype. What we can take away from this is, if the patient fits Z11 and was triple-negative, or HER2-positive, apply Z11. Z0011 was first published in 2005, and in this NCDB query ending in 2018, 50% still received a cALND, which is appalling at a time when we’re trying to omit lymph node surgery entirely in some patient populations.”

de Boniface J, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024;390(13):1163-1175.

The SENOMIC trial is a noninferiority study that compared cALND with SLNBx in 2,540 patients with clinically node-negative T1 to T3 cancers and up to two sentinel node macrometastases. The patients were randomized 1:1 to cALND or SLNB; 36% underwent mastectomy, and about 90% of patients in each arm underwent nodal radiation therapy. At five years, the relapse-free survival was high and nearly equal between the two arms.

“What I really take home is that we can omit an axillary dissection in patients with T1 and T2 tumors, patients with lymphovascular invasion, mastectomy patients, and even those with macrometastatic disease and microscopic extracapsular extension. Although the study included T1 to T3, I wouldn’t really include T3 because they made up a very small proportion of the study. I would caution that we consider regional nodal irradiation in these patients; I think the trade-off is that RNI [regional nodal irradiation] is preferable to cALND.”

Montagna G, et al. Nodal burden and oncologic outcomes in patients with residual isolated tumor cells after neoadjuvant chemotherapy (ypN0i+): the OPBC-05/ICARO study. J Clin Oncol. 2025;43(7):810-820.

This retrospective analysis of patients with stage I to III breast cancer and isolated tumor cells included 583 patients, of whom 182 (31%) had undergone cALND. At three years, there was no statistically significant difference in rates of axillary or any invasive recurrence. The authors concluded that nodal burden is low in patients with ypN0i+ (clusters of tumor cells <0.2 mm or <200 cells in a single image), and that routine cALND may not be necessary.

“Again, we’re starting to de-escalate surgery, or maybe ‘rightsize,’ for certain highly selected patients. The role of RNI is uncertain. Can we omit surgery and RNI? Again, it shouldn’t affect adjuvant systemic therapy decisions, and as with all treatment decisions, multidisciplinary input is important.”

Williams AD, et al. Should patients with hormone receptor-positive, HER2-negative breast cancer and one or two positive sentinel nodes undergo axillary dissection to determine candidacy for adjuvant abemaciclib? Cancer. 2024;130(7):1052-1060.

This query of the NCDB sought to determine the proportion of patients with up to two positive SLNs without high-risk features who had four or more positive lymph nodes on ALND and therefore would have qualified for abemaciclib (Verzenio, Eli Lilly). They found only 13% of the 1,578 patients with one or two positive SLNs had four or more involved lymph nodes, and concluded that performing cALND just to determine candidacy for abemaciclib constituted surgical overtreatment.

“My conclusions are a little more broad: that biology trumps pathology, and the recent approval of ribociclib [Kisqali, Novartis] for N0 and N+ disease seen in the NATALEE trial decreases the reliance on nodal information in the presence of other high-risk indications for the use of CDK [inhibitors].”

Ryu H, et al. A nationwide study of breast reconstruction after mastectomy in patients with breast cancer receiving postmastectomy radiotherapy: comparison of complications according to radiotherapy fractionation and reconstruction procedures. Br J Cancer. 2024;131(2):290-298.

This retrospective review looked at 4,669 breast cancer patients who underwent mastectomy with reconstruction and post-mastectomy radiation therapy, comparing complications between those who had hypofractionated fractionation (HF) and those who had conventional fractionation (CF). Overall, about 30% had HF and 70% CF, but the proportion of those undergoing HF rose between 2015 and 2020, at which point 41% were receiving HF. Ultimately, they found no difference in complications between the two groups.

“We use HF all the time for patients undergoing breast-conserving surgery, but when our mastectomy patients have an indication for radiation, traditionally they have received CF. In this study, it’s interesting that the more comfortable radiation oncologists became with HF, the more the use of it increased. The CHARM trial, presented at the 2024 San Antonio Breast Cancer Symposium, confirmed the safety data, and with a follow-up of 4.5 years revealed no significant difference in locoregional recurrence.”