This weekly update brings you the latest in breast cancer guidelines and research from the past week. We summarize guidelines and highlight key points to help patients, caregivers, and health care professionals stay current with this dynamic, evolving field. Note that both U.S. and international guidelines and research are included, so that we are inclusive of both domestic and international audiences.

The week’s top guidelines and research:

1. Biomarkers of Response to Trastuzumab Deruxtecan (DESTINY-Breast 01/02/03 Pooled Analysis)
This article looks at people with HER2-positive metastatic breast cancer treated with trastuzumab deruxtecan (T-DXd) across three DESTINY-Breast studies and groups them by how well their tumors responded. Patients whose tumors shrank a lot (complete or partial response) tended to live longer and go longer without their cancer growing than those whose tumors did not respond. The researchers also examined tumor biomarkers to see which biological features were linked with better responses to T-DXd, suggesting that these markers might help doctors predict who will benefit most. Overall, the findings support T-DXd as a strong treatment option after earlier HER2 therapies and highlight the value of using both tumor response and biomarkers to guide care.

Key message:
Patients whose tumors have higher HER2 levels tend to respond better and for longer to T-DXd.
Deep responses, including complete responses, are linked to excellent long-term outcomes without increased toxicity.

Reference: Annals of Oncology, 2025 — Read here

2. Mixed Molecular Subtypes Coexist in Estrogen Receptor–Heterogeneous Primary Breast Cancers
This study demonstrates mixed Luminal A and Luminal B molecular subtypes within estrogen receptor (ER)-intermediate primary breast cancers and reveals that ER- tumor cell populations have molecular features of endocrine resistance but chemotherapy sensitivity. These findings may explain the worse clinical outcomes of patients with ER-heterogeneous breast cancers and suggest benefit from combined endocrine and chemotherapy strategies.

Key message:
Some tumors contain both ER-high and ER-low areas, which behave differently and may require combined treatments. ER-low areas are more aggressive but respond well to chemotherapy, while ER-high areas depend more on hormones.

Reference: Journal of Clinical Oncology, 2025 — Read here

3. Field Cancerization, Accelerated Aging, and Immunosuppression in HR+ Breast Cancer
This article explains that the recent rise in hormone-sensitive and early-onset breast cancers is likely driven in part by long-term exposure to environmental chemicals that interfere with hormones, called endocrine disrupting chemicals (EDCs). These substances, found in things like industrial pollution, plastics, pesticides, and flame retardants, can build up in the body, speed up aging processes in breast tissue, damage DNA, and alter how genes are turned on and off, which can set the stage for cancer to develop earlier in life. The authors argue that EDCs also weaken the immune system’s ability to detect and destroy abnormal cells and help create “fields” of seemingly normal breast cells that are already primed to become cancerous, especially in younger women. They call for better ways to measure real-world chemical exposure over time and suggest that understanding these mechanisms could lead to new prevention and treatment strategies focused on environmental risk and epigenetic changes.

Key message:
Environmental chemicals that disrupt hormones may raise the risk of HR+ breast cancer, especially in younger women. These exposures may weaken local immunity and cause tissue changes long before cancer develops.

Reference: NPJ Breast Cancer, 2025 — Read here

4. HER2CLIMB-02: Tucatinib + T-DM1 in Previously Treated HER2+ Metastatic Breast Cancer
The Phase III study evaluating tucatinib and trastuzumab emtansine (T-DM1) showed improved progression-free survival versus T-DM1 alone. Patients were randomly split into two groups: one received T-DM1 plus tucatinib, and the other received T-DM1 plus a placebo. The group that received tucatinib went about 2 months longer on average before their cancer grew again, and this benefit was also seen in people whose cancer had spread to the brain, but they had more serious side effects, especially liver-related lab changes. Overall, adding tucatinib to T-DM1 improved the time patients lived without their disease getting worse, with side effects including mainly diarrhea and liver enzyme increases.

Key message:
Adding tucatinib to T-DM1 can delay cancer progression, including in patients with brain involvement.
Side effects are more common, mainly diarrhea and liver enzyme increases, so monitoring is important.

Reference: Annals of Oncology, 2025 — Read here

5. Association between type and location of germline BRCA1/2 pathogenic or likely pathogenic variants with phenotype and prognosis on young patients with breast cancer: Results from an Internantional Cohort Study
This international cohort study examined 3,294 young women (under 40 years old) with BRCA1/2 variants. Researchers found that where exactly in those genes the variant is located can affect how the cancer develops and what the prognosis is. Not all BRCA1/2 mutations are the same. The “type and location” of the mutation appears linked to differences in how aggressive the cancer may be and how patients do over time. This information could help doctors give more personalized advice and treatment for young patients with inherited BRCA mutations.

Key message:
Not all BRCA mutations carry the same clinical risk, supporting variant-specific counseling.

Reference: Annals of Oncology, 2025 — Read here

6. Dynamic Tumor-Infiltrating Lymphocytes Predict Survival in HR+/HER2- Early Breast Cancer: A Pre-to-Post Neoadjuvant Chemotherapy Study
This study looked at a group of women with HR+/HER2- early-stage breast cancer who received chemotherapy before surgery. The researchers measured how many immune cells, called tumor-infiltrating lymphocytes (TILs), were in the tumor before and after chemo, then tracked their health over time. They found that having higher TILs before treatment (or developing more TILs after chemo) was linked with worse survival, while a drop in TILs after treatment was associated with better outcomes.

Key message:
In HR+ breast cancer, having more immune cells (TILs) in the tumor is linked to a worse prognosis, which is opposite to what we see in HER2-positive and triple-negative tumors, where high TILs are usually favorable. If these immune cells increase after chemotherapy, the risk of the cancer returning becomes even higher.

Reference: Breast Cancer Research, 2025 — Read here