Novel treatment protocols are demonstrating significant improvements in overall survival and progression-free survival for breast cancer patients while targeted therapies continue to expand treatment options. The 2025 clinical landscaped has witnessed precision medicine hitting its stride and delivering unprecedented hope — personalized treatments that zero in on a patient’s distinct genetic fingerprint, paving the way for not just longer lives, but healthier and more vibrant futures.

“We have changed the way we practice tremendously because of recent breakthroughs,” says radiation oncologist Youssef Zeidan, M.D., Ph.D., a breast cancer specialist at Lynn Cancer Institute based at Boca Raton Regional Hospital, part of Baptist Health. “And new clinical trials are giving us further insights that we are using to develop more personalization in radiation therapy.”

Approximately 376,000 women in the U.S. will be diagnosed with breast cancer this year, according to the American Cancer Society. Studies on treatment trends reveal that about half of them will receive radiation therapy as part of their treatment.

De-escalation strategies in radiation therapy

Clinical research is examining optimal patient selection for radiation therapy, with several pivotal trials informing evidence-based de-escalation strategies:

• Omitting Regional Nodal Irradiation after Response to Neoadjuvant Chemotherapy – This landmark NSABP B-51 clinical trial has investigated the safety of omitting regional lymph node irradiation after chemotherapy has successfully cleared nodal disease. “What this means,” Dr. Zeidan says, “is that some patients who respond well to initial treatment can safely omit nodal radiation, resulting in fewer side effects.” The findings have been incorporated into the recently published national guidelines for radiation therapy, Postmastectomy Radiation Therapy: An ASTRO/ASCO/SSO Clinical Practice Guideline, co-authored by Dr. Zeidan.
• TAILOR-RT (MA39) Trial: Regional Radiotherapy in Biomarker Low-Risk Node Positive and Breast Cancer – Lynn Cancer Institute and Baptist Health Miami Cancer Institute are participating in this study, taking a closer look at which patients with low-risk characteristics actually need extensive radiation treatment. “We are currently enrolling patients who have a limited number of positive lymph nodes in the axilla, have no evidence of metastases and a low Oncotype Recurrence Score,” he says. “We hope this trial, based on a molecular test, helps us risk-stratify patients who need more-intense radiation and those who are good candidates for de-escalation.”
• NRG CC-016 Clinical Trial – Even for patients with ductal carcinoma in situ (DCIS), an early form of breast cancer, the field is moving toward more-individualized care. The Institutes will be participating in this soon-to-open study (NRG CC-016) that is using a molecular test to determine who needs radiation therapy after lumpectomy for DCIS.
• Breast Re-irradiation After Second Ipsilateral Lumpectomy (BRASIL) trial – Dr. Zeiden is the principal investigator of this trial, currently open at Lynn Cancer Institute and Miami Cancer Institute. It is exploring options for early-stage breast cancer survivors who experience a second breast cancer event in the same breast. “We are seeing an increase in such cases because breast cancer survivors are living longer,” he says. “For many years, the standard of care was a mastectomy, but mastectomy comes with many side effects physically and mentally for these older patients, so we are looking at the safety and efficacy of another lumpectomy followed by another round of radiation therapy.”

Advances in precision drug therapies

While radiation therapy advances are reshaping one aspect of breast cancer treatment, equally exciting progress is happening in the realm of systemic therapies. Beyond the operating room and radiation suite, oncologists are wielding a new arsenal of sophisticated drugs that work at the molecular level to target cancer cells with remarkable precision. These innovative treatments — including antibody drug conjugates (ADCs), immunotherapy and CDK4/6 inhibitors — are improving outcomes for patients across all stages of breast cancer, offering new pathways to a disease-free life and extending quality time with loved ones.

“ADCs have really transformed care for patients with advanced breast cancer, offering longer disease control, improved survival and better quality of life compared to standard chemotherapy,” says Reshma Mahtani, D.O., chief of breast oncology at Miami Cancer Institute.

ADCs are like a Trojan horse, acting as scouts and seeking out and targeting cancer cells with a very toxic payload that releases within the cell. “At Baptist, we’re leading the SERIES study, which is evaluating patients with hormone receptor-positive, HER2-low metastatic breast cancer who have already been treated with one ADC, trastuzumab deruxtecan, and then go on to receive another, sacituzumab govitecan,” Dr. Mahtani says. “This is one of the first prospective trials to study how ADCs work when given sequentially — something that’s urgently needed to guide care in the real world.”

Immunotherapy and targeted inhibitors expand the arsenal

In addition to ADCs, immunotherapy is now showing survival benefits for women with aggressive triple-negative breast cancer in the early-stage setting. Additionally, CDK4/6 inhibitors, drugs that block specific proteins that help cancer cells divide and grow, have transitioned from use in advanced disease management into earlier stages, reducing the risk of recurrence for many women with hormone receptor-positive breast cancer.

“Each of these represents real progress because they move us closer to more personalized, effective and less toxic treatments,” Dr. Mahtani notes.

At the meeting of the American Society of Clinical Oncology, Dr. Mahtani presented research evaluating women age 70 and older with early-stage hormone receptor-positive, HER2-negative breast cancer, who participated in an observational registry trial called FLEX. This demographic has been historically underrepresented in clinical trials. “We know that older women are often less likely to get chemotherapy because of concerns about side effects, and they’ve been underrepresented in past studies,” she says.

The study utilized the MammaPrint genomic test to help identify which patients are at higher risk of recurrence. “We found that women 70 and older with MammaPrint High 2 cancers may, in fact, benefit from chemotherapy, with about an 11 percent improvement in recurrence-free survival at three years. This highlights that genomic testing can be very helpful in guiding personalized treatment decisions for older patients and that some still benefit from chemotherapy. Therefore, discussions surrounding the use of chemotherapy in these patients should be individualized.”

The next step in the research, she adds, is to expand the analysis to look at how other health conditions affect treatment decisions and outcomes in older patients. “Since many women over 70 have other medical issues, understanding this impact is important for tailoring care,” she says.

Research integration into clinical practice

For Drs. Zeidan and Mahtani and their teams, research remains integral to patient care. “Every new discovery has the potential to improve outcomes and change lives,” Dr. Mahtani says. “It’s how we push the field forward. Every day, I use research to guide treatment decisions, explore the latest clinical trials and apply insights from genomics and translational studies to tailor therapies. For my patients, this means care that is not just evidence-based, but truly personalized to give them the best chance for a positive outcome.”

“It’s an exciting time to engage with our colleagues on a national and international level,” Dr. Zeidan says. “I am a better physician because I have these opportunities to be involved with research and to provide cutting-edge care for our patients.”

For more information on Baptist Health Cancer Care research, click here.