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In this episode, CancerNetwork® spoke with Joseph S. Wallins, MD, MPH, cardiology fellow at Weill Cornell Medicine, about a 

review of cardiotoxicities associated with breast cancer treatment

 he coauthored in the June 2025 issue of 

 titled “Cardio-Oncology Considerations for Breast Cancer: Risk Stratification, Monitoring, and Treatment.” Therein, he touched upon data for risk stratification tools for oncologists as well as the development of cardiovascular testing for individual treatment regimens.

Wallins discussed the basis for conducting the systemic review as well as noteworthy cardiotoxicities associated with specific classes of breast cancer therapies. Specifically, he highlighted an increase in cancer remission and survivorship for breast cancer, which has, in turn, created alternative health risks affecting survival outcomes, such as cardiovascular risks. Citing findings from a study showing a nearly 2-fold risk in cardiovascular-related fatalities for survivors of breast cancer vs the general population, he suggested that the review was warranted to identify cardiotoxicities, strategies for preventing and managing them, and tools for risk stratification and monitoring.

Wallins further outlined considerations for optimizing risk stratification and monitoring strategies in patients at risk of experiencing cardiovascular toxicities as well as treatments that may help with their prevention or mitigation. To that end, he discussed identifying patients who are at a higher risk before initiating treatment and outlined risk assessment tools that serve to do so. Furthermore, he suggested that patients who experience a greater than moderate risk for cardiovascular issues should undergo cardioprotective strategies and have in-depth conversations with providers regarding treatment risks.

He concluded by highlighting future steps to enhance cardiovascular outcomes for patients with breast cancer, among additional key takeaways. Of note, Wallins expressed that genetic testing may help elucidate cardiomyopathy-associated genes while calling for a more personalized approach to risk stratification and more sensitive and specific imaging techniques to better identify patients at risk. Finally, he emphasized a need for up-front risk assessment to identify patients at a higher risk who could benefit from additional testing as well as more pronounced collaboration between oncologists and cardiologists.

Bradshaw PT, Stevens J, Khankari N, Teitelbaum SL, Neugut AI, Gammon MD. Cardiovascular disease mortality among breast cancer survivors. 

. 2016;27(1):6-13. doi:10.1097/EDE.0000000000000394

Up-front risk stratification for additional cardiovascular testing may help mitigate cardiovascular toxicities in breast cancer treatment.

Cardiovascular Considerations in Breast Cancer Treatment and Survivorship

In this episode, CancerNetwork® spoke with breast oncologists Heather McArthur, MD; Erika Hamilton, MD; Hope Rugo, MD; and Paolo Tarantino, MD, PhD, about advances in breast cancer. These developments included recent drug approvals and ongoing research for therapeutic approaches, particularly in the areas of antibody-drug conjugates (ADCs) and CDK4/6 inhibitors, based on presentations they gave at the 

 International Congress on the Future of Breast Cancer® (IBC) East in New York, New York.

Initially, McArthur, Komen Distinguished Chair in Clinical Breast Cancer Research at the Harold C. Simmons Comprehensive Cancer Center, discussed immunotherapy use in high-risk triple-negative and HER2-positive disease, the evolving role of adjuvant CDK4/6 inhibition in HER2-negative breast cancer, and potentially transformative advancements in early breast cancer treatment.

She highlighted the FDA approval for pembrolizumab (Keytruda) in early-stage triple-negative breast cancer; promising clinical trials in high-risk, early-stage estrogen receptor (ER)–positive breast cancer; and data from an investigator-initiated trial to treat HER2-positive disease. Additionally, she highlighted an 8.5% improvement in pathological complete response with pembrolizumab added to immunotherapy in the phase 3 KEYNOTE-756 trial (NCT03725059), adding that a further event-free survival benefit may complicate the landscape for CDK4/6 inhibition based on lung and liver toxicities associated with the coadministration of these inhibitors with immunotherapy.

McArthur expressed further excitement for ADC-based combinations for triple-negative disease as well as the high-risk residual disease setting. In addition, she highlighted potential advancements in de-escalation strategies and further considerations for ADCs in the HER2-positive and hormone receptor (HR)–positive spaces.

Hamilton, director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute, highlighted emerging therapies for early breast cancer as well as her use of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) given their recent approvals in various breast cancer subtypes. She also touched upon challenges with respect to the implementation of new therapies for early breast cancer into clinical practice.

She initially highlighted new data from the 

2025 American Society of Clinical Oncology Annual Meeting

 Specifically, findings showed that vepdegestrant, an oral proteolysis-targeting chimera, exhibited an efficacy advantage over fulvestrant (Faslodex) in patients with 

-mutant ER-positive, HER2-negative advanced or metastatic disease. Moreover, she highlighted data from the 

 trial of T-DXd in various combinations for patients with HER2-positive metastatic breast cancer.

Hamilton further highlighted her implementation of T-DXd into clinical practice, citing her use of the agent in patients with metastatic disease, including those with HER2-low and HER2-ultralow breast cancer. She further differentiated dato-DXd from T-DXd, suggesting that they were different classes of drugs due to their different targets: TROP2 vs HER2. She concluded by highlighting an unmet need regarding sustained benefit from endocrine therapy in HR-positive disease as well as for ADC sequencing and mechanisms of resistance.

Afterward, Rugo, division chief of breast medical oncology, director of the Women’s Cancer Program, and professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, discussed efficacy and safety considerations for CDK4/6 inhibitors in early breast cancer treatment. Specifically, she highlighted their high tolerability despite adverse effects and costs associated with their use. Rugo further touched upon a reduction of recurrence rates associated with CDK4/6 inhibition, although longer-term follow-up data were warranted to optimize the duration of therapy and elucidate survival outcomes.

Finally, Tarantino, a research fellow at the Dana-Farber Cancer Institute, concluded by discussing sequencing strategies for ADCs as well as which breast cancer settings or patient populations will experience the greatest impact with this treatment modality. Tarantino discussed his use of the “sandwich strategy,” where he switches the mechanism of action of treatment after using a TOPO1 ADC. Furthermore, Tarantino highlighted data from the DESTINY-Breast09 and phase 3 ASCENT-04 (NCT06100874) trials, which displayed the enhanced efficacy of 2 ADC combination therapies.

 He concluded by discussing future considerations for combining multiple ADCs.

Cardoso F, O'Shaughnessy J, Liu Z, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2- breast cancer: a randomized phase 3 trial. 

 2025;31(2):442-448. doi:10.1038/s41591-024-03415-7

Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. 

. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000

Tolaney S, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09. 

Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 

. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109

Leading experts in the breast cancer field highlight the use of CDK4/6 inhibitors, antibody-drug conjugates, and other treatment modalities.

Advancements and Evolving Strategies in Breast Cancer Treatment at IBC East

, Oluwadamilola “Lola” Fayanju, MD, MA, MPHS, FACS, discussed the key findings from 

a study she published in JAMA Network Open

which demonstrated that most patients with inflammatory breast cancer do not receive all available types of guideline-concordant care they are eligible for. Additionally, data showed disparities regarding receipt of modality-specific therapy among patients who were Black, Asian, Hispanic, or other racial minority populations.

Based on these findings, Fayanju highlighted potential next steps for mitigating these gaps in care for certain patients with breast cancer. These strategies included revising stringent inclusion criteria for clinical trial enrollment, which may disproportionately exclude racial minority populations who have higher rates of diabetes or other medical conditions. Fayanju also emphasized educating clinicians across different oncology specialties to recognize how different populations present with inflammatory breast cancer and better understand the context in which patients receive treatment.

“I hope [the study] makes some people angry…Frustration can be a wonderful fuel,” Fayanju stated regarding her research. “[By] recognizing that there isn't as much guideline-concordant care receipt amongst all people as there should be and the hope that's provided when we achieve concordant care, we can mitigate and eliminate racial disparities. I hope [that] will motivate people to think about how we can get more guideline-concordant care to more people and how we can incorporate diverse populations in the development of guidelines for concordant care at the beginning. Then, how can we also develop treatments that achieve efficacious results across diverse populations?”

Fayanju is the Helen O. Dickens Presidential Associate Professor, chief in the Division of Breast Surgery at Penn Medicine, surgical director of Rena Rowan Breast Center, director of Health Equity Innovation at Penn Center for Cancer Care Innovation (PC3I), and senior fellow at Leonard Davis Institute of Health Economics (LDI), Perelman School of Medicine at the University of Pennsylvania.

Tadros A, Diskin B, Sevilimedu V, et al. Trends in guideline-concordant care for inflammatory breast cancer. JAMA Netw Open. 2025;8(2):e2454506. doi:10.1001/jamanetworkopen.2024.54506

Findings highlight a need to incorporate diverse populations when developing guideline-concordant breast cancer care to achieve efficacy for all patients.

Eliminating Racial Disparities in Guideline-Concordant Breast Cancer Care

2024 San Antonio Breast Cancer Symposium (SABCS),

 Paolo Tarantino, MD, and Matteo Lambertini, MD, PhD, co-hosted a live X Space with CancerNetwork

 and spoke about updated trial findings that may impact the breast cancer treatment paradigm.

Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School. Lambertini is an associate professor and consultant in medical oncology at the University of Genova – IRCCS Policlinico San Martino Hospital in Genova, Italy.

Tarantino and Lambertini highlighted data from various studies that investigators presented at the Symposium, which included results on the use of treatment modalities such as antibody drug conjugates and CDK4/6 inhibitors. Some presentations of interest included the following:

Phase 3 DESTINY-Breast06 Trial (NCT04494425)

Patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer were assigned to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or physician’s choice of therapy.

Treatment with T-DXd improved progression-free survival (PFS) among patients with a time to progression on frontline endocrine therapy of less than 6 months (HR, 0.38; 95% CI, 0.25-0.59), 6 to 12 months (HR, 0.69; 95% CI, 0.43-1.12), and more than 12 months (HR, 0.67; 95% CI, 0.51-0.88).

PFS improved with T-DXd regardless of disease burden.

Investigators evaluated 3 treatment arms—imlunestrant (LY3484356) monotherapy, fulvestrant (Faslodex) or exemestane (Aromasin), and imlunestrant in combination with abemaciclib (Verzenio)—among patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.

Across the overall population, imlunestrant monotherapy improved PFS compared with standard endocrine therapy (HR, 0.87; 95% CI, 0.72-1.04; 

Imlunestrant plus abemaciclib also showed a PFS improvement vs endocrine therapy across the overall population (HR, 0.57; 95% CI, 0.44-0.73; 

Phase 2 SOLTI-VALENTINE Trial (NCT05569811)

Patients with primary operable HR–positive/HER2-negative breast cancer were assigned to receive patritumab deruxtecan (HER3-DXd) alone, HER3-DXd plus letrozole (Femara), or standard multiagent chemotherapy.

HER3-DXd monotherapy yielded a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%); the respective rates in the chemotherapy arm were 4.2% (95% CI, 0.1%-21.1%) and 70.8% (95% CI, 48.9%-87.4%).

Combining HER3-DXd with letrozole produced a pCR rate and ORR of 2.1% (95% CI, 0.1%-11.1%) and 81.3% (95% CI, 67.4%-91.1%), respectively.

Bardia A, Hu X, Dent R, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. Abstract LB1-04.

Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): results of the phase 3 EMBER-3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. Abstract GS1-01.

Oliveira M, Pascual T, Parraga KA, et al. Neoadjuvant HER3-DXd alone or in combination with letrozole for high-risk HR+/HER2- early EBC: Primary results of the randomized phase II SOLTI VALENTINE trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. Abstract LB1-06.

Paolo Tarantino, MD, and Matteo Lambertini, MD, PhD discuss findings related to CDK4/6 inhibitors and antibody drug conjugates presented at SABCS 2024.

SABCS 2024 Data Show ‘Great Steps Forward’ in Breast Cancer Care

CancerNetwork® spoke with Rachel A. Greenup, MD, MPH, an associate professor of surgery (oncology), section chief of Breast Surgery, and co-director of the Center for Breast Cancer at the Yale School of Medicine, about the rationale behind conducting a 

study evaluating the lived experiences among women of color following breast cancer mastectomy

, as well as data collection strategies employed during the study and key themes outlined in questionnaire responses.

First, Greenup, senior author of the study, emphasized that disparities persist for women of color following mastectomy for breast cancer, both in those seeking breast reconstructive surgery and those choosing to forego it, which is an act called “living flat.” She explained that many of the stories behind these disparities were left untold, and this study was seeking to unearth them.

She then explained that women of color who underwent a mastectomy for breast cancer were sampled for the study. The patient population included women from her institution and survivors willing to share their experiences.

Expressing that her team strove to let the stories of these women speak for themselves, she discovered 2 major findings during her research. The first theme that emerged was a cultural stigma surrounding cancer diagnoses among minority groups, which impact knowledge of family history as well as timely screening, care, and support for their disease. The second major theme that her study revealed was spirituality as a driver for many of the decisions following mastectomy.

Greenup further emphasized a need for cultural, racial, and ethnic inclusion during clinical trials, which extends to anticipating differences in cancer developments among diverse populations. She concluded by encouraging all patients to share their family history of cancer, regardless of background, as it can impact screening and prevention measures.

“I would encourage all families and all individuals from different cultural backgrounds to share their family history of cancer. It has a critical impact in terms of screening and cancer prevention for other family members,” Greenup said. “It can be difficult to have those conversations, but it is information that can be powerful for future prevention.”

Khubchandani JA, Suttiratana SC, Washington R, et al. Living flat: stories from women of color after mastectomy. Ann Surg Oncol. Published online October 15, 2024. doi:10.1245/s10434-024-16337-y

A study evaluating disparities in breast reconstructive surgery sought to assess the impact of culture, race, and ethnicity in minority groups.

Reducing Post-Mastectomy Disparities in Breast Cancer Minority Populations

2024 American Society of Clinical Oncology (ASCO) Annual Meeting,

 Neil M. Iyengar, MD, and Paolo Tarantino, MD, co-hosted a live X Space with CancerNetwork

 and discussed the latest trial updates that may impact clinical practice in the breast cancer field.

Iyengar is an associate attending physician at Memorial Sloan Kettering Cancer Center and a co-editor-in-chief of 

Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School.

Iyengar and Tarantino discussed data regarding several trials and studies presented at the meeting. These presentations included:

Investigators evaluated treatment with trastuzumab deruxtecan (T-DXd; Enhertu) compared with investigator’s choice of chemotherapy among patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer.

The median progression-free survival (PFS) was 13.2 months with T-DXd compared with 8.1 months in patients who received chemotherapy across the HER2-low population (HR, 0.62; 95% CI, 0.51-0.74; 

Primary analysis overall survival (OS) data show favorable trends in the T-DXd arm across the HER2-low group (HR, 0.83; 95% CI, 0.66-1.05; 

 = .1181) and the intent-to-treat (ITT) population (HR, 0.81; 95% CI, 0.65-1.00). However, the OS data only reached 40% maturity at the time of the analysis.

Patients with HR-positive, HER2-negative breast cancer and disease progression on CDK4/6 inhibitors and endocrine therapy were assigned to receive abemaciclib (Verzenio) or matched placebo plus fulvestrant (Faslodex).

The median PFS per investigator assessment was 5.6 months (95% CI, 5.4-9.2) with abemaciclib-based therapy vs 3.9 months (95% CI, 3.7-5.4) with placebo plus fulvestrant (HR, 0.66; 95% CI, 0.48-0.91; 

The investigator-assessed objective response rate (ORR) was 17% vs 7% in each respective arm.

Investigators assessed sacituzumab govitecan-hziy (Trodelvy) alone or in combination with pembrolizumab (Keytruda) for HR-positive, HER2-negative metastatic breast cancer regardless of PD-L1 status.

Combination therapy yielded a numerical improvement in median PFS (8.12 months; 95% CI, 4.51-11.12) compared with sacituzumab govitecan monotherapy (6.22 months; 95% CI, 3.85-8.68), although this improvement did not reach statistical significance (HR, 0.81; 95% CI, 0.51-1.28; 

Immature OS data presented at the meeting highlighted a median OS of 18.52 months (95% CI, 16.55-not applicable [NA]) vs 17.96 months (95% CI, 12.50-NA) in each respective arm (HR, 0.65; 95% CI, 0.33-1.28; 

Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): primary results from DESTINY-Breast06 (DB-06). 

. 2024;42(suppl 17):LBA1000. doi:10.1200/JCO.2024.42.17_suppl.LBA1000

Kalinsky K, Bianchini G, Hamilton EP, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: primary outcome of the phase 3 postMONARCH trial. 

. 2024;42(suppl 17):LBA1001. doi:10.1200/JCO.2024.42.17_suppl.LBA1001

Garrido-Castro A, Kim, SE, Desrosiers J, et al. SACI-IO HR+: a randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. 

. 2024;42(suppl 17):LBA1004. doi:10.1200/JCO.2024.42.17_suppl.LBA1004

American Society of Clinical Oncology Annual Meeting (ASCO)

Neil M. Iyengar, MD, and Paolo Tarantino, MD, discuss updated data on agents such as T-DXd and abemaciclib in breast cancer presented at 2024 ASCO.

Breast Cancer

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