New hormonal therapy progress, plus less treatment for some | SABCS 2025
- 12/15/25
At this year’s San Antonio Breast Cancer Conference, researchers shared new advances for both early-stage and metastatic breast cancer. Below we share four highlights — a new hormonal therapy on track for FDA approval, new combination therapies, and an indication that some early-stage breast cancers can be safely treated with less surgery — that offer hope for more options, more time, and less treatment when it’s safe.
New hormonal therapy for ER+, HER2-negative early-stage breast cancer on track for FDA approval
Therapy: Giredestrant
Type of medication: Hormonal therapy (oral SERD)
How is it used: To treat early-stage HR+/ HER2-negative breast cancer following chemotherapy
How is it different: Giredestrant will likely be the first new hormonal therapy approved by the FDA to treat early-stage breast cancer in 20 years. It is in the same family as fulvestrant but taken as a pill.
What did the study find: Giredestrant outperformed aromatase inhibitors and tamoxifen in people with early-stage ER+, HER2-negative breast cancer. People taking giredestrant had a 30% less risk of cancer growth compared to participants taking other hormonal therapies. This represented a lower absolute risk of cancer growth of 2.7% due to the high treatment success for this type and stage of breast cancer.
What are the side effects: Joint pain and menopausal symptoms were the most common side effects. Fewer people in the giredestrant group stopped treatment due to side effects than in the aromatase inhibitor/tamoxifen group. Of people taking giredestrant, 11% had mild bradycardia or slow heart rate with no symptoms.
Study details: The global phase III randomized control trial lidERA trial included 4,140 pre- and post-menopausal women with early-stage, ER+, HER2-negative breast cancer. Half of the participants had stage II disease, and nearly 70% were considered at high risk for recurrence.
Key takeaway: This drug is poised to be a new standard treatment. Questions remain about the cost, who will get it, and when the drug will be given.
Maintenance therapy with tucatinib extends time without cancer growth in HER2+ metastatic breast cancer
Therapy: Tucatinib given with trastuzumab and pertuzumab
Type of medication: Maintenance combination therapy
How it is used: To treat metastatic HER2+ breast cancer
How it is different: With the addition of tucatinib, the combination therapy targets cancer cells in multiple ways.
What did the study find: At two years, people who received tucatinib on top of the standard maintenance therapy for HER2+ metastatic breast cancer (MBC) went on average 8.6 months longer without cancer growth (24.9 months versus. 16.3 months). The benefit was seen in people with ER-positive disease (+6.9 months) and ER-negative disease (+12.3 months). Early results suggest that the addition of tucatinib may extend life. Based on a small subsample, it also appears that the drug may slow the growth of brain metastases.
What are the side effects: Mild diarrhea was the most common side effect experienced by study participants. People taking tucatinib also experienced nausea, changes in liver enzymes, joint pain, and fatigue. Study participants taking tucatinib were more likely to have serious side effects compared to those given a placebo (42% versus 24%).
Study details: The phase III HER2CLIMB-05 clinical trial tested the addition of tucatinib to the standard combination therapy of trastuzumab and pertuzumab for people with HER2+ metastatic breast cancer. The study included 654 women, most with de novo metastatic disease. People with asymptomatic brain metastases were eligible. Participants were randomized to receive tucatinib or a placebo in addition to the dual combination therapy following first treatment with trastuzumab, pertuzumab, and chemotherapy. Participants with HR+ disease also received hormonal therapy.
Key takeaway: The addition of tucatinib reduced the risk of cancer growth or death by 36%. Once it’s approved by the FDA, this combination therapy will represent a new maintenance therapy option for this group, giving people with HER2+ MBC more time off chemotherapy.
Five years later: Omitting sentinel node biopsy is safe for very early HR+ breast cancers
Therapy: Sentinel lymph node biopsy (SLNB)
Type of medication: Diagnostic surgical procedure
How is it used: To learn more about the cancer and its likelihood of returning after treatment
How is it different: This study addresses overtreatment. It confirms that sentinel lymph node biopsy is not needed for most people with cT1-2 N0 (stage IA or stage IIA) breast cancer who undergo lumpectomy and radiation.
What did the study find: After five years, the risk of regional recurrence was low both for people who had SLNB and for those who did not (96.6% versus 94.2%). The small difference of 2.35% is below the 5% needed to confirm that the less invasive approach is acceptable.
What are the side effects: Omitting SLNB reduces the risk of post-surgery side effects, such as potential scarring and discomfort, and the long-term potential of lymphedema, painful swelling caused by a buildup of lymph fluid.
Study details: The phase III randomized BOOG 2013-08 trial was conducted at 25 sites in the Netherlands. The 1,733 participants had diagnoses of stage IA and stage IIA breast cancer (small tumors with no node involvement). While all major breast cancer subtypes were represented, most participants were over 50 and diagnosed with HR+ breast cancer. Half the people in the trial did not receive any systemic drug therapy, including hormonal therapy.
Key takeaway: This study shows that it may be safe to omit SLNB in very early-stage, node-negative HR+ breast cancers treated with lumpectomy and radiation, regardless of whether hormonal therapy is taken. The research team is awaiting more data before making a conclusion, which can then be used to determine future standard of care.
Imlunestrant effective against HR+/HER2-negative advanced breast cancer
Therapy: Imlunestrant (Inluriyo) with or without abemaciclib
Type of medication: Hormonal therapy alone or with CDK 4/6 inhibitor therapy
How is it used: To treat HR+, HER2-negative advanced breast cancer
How is it different: Imlunestrant is an oral selective estrogen-receptor therapy (SERD), a more powerful type of SERD. It is approved for use alone in ESR1-mutant HR+/HER2-negative advanced breast cancers. Abemaciclib is also a pill, so the two drugs together offer an entirely oral option.
What did the study find: Imlunestrant taken with or without abemaciclib was more effective than the standard treatment for HR+/HER2-negative advanced breast cancer (ABC). With an additional year of data, the results that led to FDA approval still hold. Imlunestrant alone extended survival by 11.4 months and delayed the need for chemo by 5.4 months in the ESR1-mutant group. At longer follow-up, imlunestrant plus abemaciclib nearly doubled the time without cancer growth compared to imlunestrant alone (10.9 versus 5.5 months). Imlunestrant plus abemaciclib is effective for HR+/HER2- ABC regardless of ESR1 or PIK3 status.
What are the side effects: Common side effects are stomach distress, including diarrhea, changes in blood cell counts, and fatigue. Most side effects are mild. Side effects are more common and/or a little worse with the addition of abemaciclib.
Study details: The phase III EMBER-3 compared three treatments for HR+/HER2-negative ABC: imlunestrant alone, imlunestrant plus abemicicib, and fulvestrant/exemestane. The study of 874 people led to FDA approval of imlunestrant.
Key takeaway: If you have HR+/HER2-negative advanced breast cancer that is no longer responding to estrogen therapy, ask your doctor about imlunestrant. Discuss the pros and cons of taking imlunestrant alone or with abemaciclib.
Our SABCS coverage
- Control what you can control: What research tells us can reduce your risk of breast cancer, recurrence, and support better quality of life
- New hormonal therapy progress, plus less treatment for some
- What’s next for metastatic breast cancer treatments?
- Breast cancer is personal: Your treatment should be, too
Watch our recap!
Harold J. Burstein, MD, PhD, breaks down the most meaningful breast cancer research updates from this year’s symposium, in conversation with moderator Caroline Koffke, RN, BSN, OCN, LBBC’s Director, Educational and Healthcare Provider Programs.
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