The I-SPY2 Trial is transforming breast cancer treatment, offering new insights into pre-surgery chemotherapy for invasive lobular breast cancer (ILC). Presented at the 2025 American Society of Breast Surgeons (ASBrS) meeting, this study explores surgical outcomes and lymph node response in high-risk tumors. In an exclusive interview, Rita Mukhtar, MD, a breast surgeon at UCSF, shares how the MammaPrint assay enhances breast cancer care by identifying ILC patients who benefit from chemotherapy. Therefore, this 2025 breakthrough is shaping personalized treatment for breast cancer.
Understanding the I-SPY2 Trial
The I-SPY2 Trial (2010–2021) tests pre-surgery chemotherapy to improve breast cancer treatment in stage II-III patients with high-risk tumors, identified by the MammaPrint assay (Page 5). It compares lobular and ductal outcomes, focusing on surgery and lymph node response. Because the trial allows flexible surgical choices, it mirrors real-world decisions (Page 6). Thus, it reveals preferences in breast cancer care.
Breast Conservation Surgery Results
Comparable Surgery Rates
The trial found no difference in breast conservation surgery (BCS) rates between lobular and ductal patients, advancing breast cancer treatment options (Page 9). Unlike past studies showing higher mastectomy rates for ILC, I-SPY2 suggests patient choice drives outcomes. Moreover, mastectomy rates were high for both groups.
“Patients with lobular breast cancer in the I-SPY2 Trial had the same rate of breast conservation surgery as those with ductal breast cancer,” says Rita Mukhtar, MD. (00:00–00:09)
Surgical Margin Challenges
Higher Positive Margins in ILC
Lobular patients had a 20% positive margin rate during BCS, compared to 7–8% for ductal patients, impacting breast cancer treatment success (Page 16; 01:14–01:26). This occurs because ILC grows diffusely, often extending beyond mammogram, ultrasound, or MRI findings.
“Lobular breast cancers grow in a diffuse pattern, extending beyond imaging,” explains Rita Mukhtar, MD. (00:53–01:02)
Lymph Node Response
Strong Nodal Response
The trial reported a 40.2% nodal pathologic complete response (pCR) rate in lobular patients, higher than prior ILC studies, advancing treatment for breast cancer (Page 13; 01:32–02:17). Because MammaPrint high-risk tumors, especially High 2, showed strong chemotherapy response, the difference from ductal rates was not significant.
“The 40% nodal pCR rate in the lobular group was not statistically different from the ductal group,” notes Rita Mukhtar, MD. (02:17–02:25)
Axillary Surgery Trends
More Lymph Node Dissections
Among node-negative patients, lobular cases had more axillary lymph node dissections (ALND) (p=0.9, Page 11). This is because ILC often presents with larger tumors and nodal involvement, complicating breast cancer treatment (04:06–04:15).
Treatment Decision Dilemma
Chemotherapy or Surgery First?
Deciding between pre-surgery chemotherapy and immediate surgery for ILC is complex, a key challenge in breast cancer care (Page 2). Lobular tumors often present larger with positive nodes, suggesting chemotherapy to shrink them (04:12–04:22). However, ILC’s lower growth rate reduces chemotherapy response (04:26–04:48). Therefore, MammaPrint helps identify responsive patients.
“It’s hard to know if chemotherapy will shrink a stage three lobular tumor or clear lymph nodes,” says Rita Mukhtar, MD. (04:51–05:04)
Surgical Implications
Primary surgery may require mastectomy or ALND (05:10–05:17). Thus, chemotherapy is appealing when effective, improving breast cancer treatment outcomes.
Personalizing Treatment with MammaPrint
Targeting Responsive Tumors
The MammaPrint assay pinpoints high-risk tumors likely to respond to chemotherapy, enhancing treatment for breast cancer. Moreover, High 2 tumors showed the best nodal pCR rates (03:28–03:36). Despite ILC’s diverse subtypes (Page 3), MammaPrint is effective, though a lobular-specific test could refine results.
“MammaPrint helps identify tumors likely to respond to chemotherapy,” says Rita Mukhtar, MD. (02:46–02:59)
Future Directions for ILC
Ongoing Challenges
ILC’s diverse subtypes, diffuse growth, and limited high-risk cases pose challenges for breast cancer treatment (Page 3; 03:40–03:46). Furthermore, higher positive margins need better imaging or surgical methods (00:50–01:02).
Next Steps in Research
Future studies should develop lobular-specific assays and reduce positive margins to optimize breast cancer care.
Key Moments:
- 00:00–00:34: Surgery rates
- 00:38–01:26: Margin challenges
- 01:26–02:38: Nodal response
- 04:01–05:29: Treatment choices
Conclusion
The 2025 I-SPY2 Trial advances breast cancer treatment, showing similar BCS rates for lobular and ductal cancers but higher margins and ALND in ILC. Because MammaPrint identifies chemotherapy-responsive tumors, it’s key to personalized care. Moreover, ongoing research will improve ILC outcomes. Stay updated on cancer breakthroughs.
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Related Links:
https://www.breastsurgeons.org