Lifting the veil of early-stage breast cancer

Hello everyone. My name is Dr. Hattem Solomon. I'm an associate member in the breast on College in Immunology departments at the Moffitt Cancer Center. I'm also the medical director of the clinical trials office as well.

Objectives

Our agenda today and objectives are to learn about advances in the medical management of early-stage breast cancer, with a particular focus on understanding how Imaging advances and Radiology input from our colleagues can affect our Management in significant ways. We also want to explore some of the emerging data around escalation and de-escalation strategies that incorporate and rely on Imaging data.

Case 1: Hormone Receptor Positive, HER2 Negative Early Stage Breast Cancer

Summary

Our patient is a 53-year-old female, premenopausal, presenting with an enlarging palpable mass in the left breast for approximately four months. On exam, the mass measured 2.1 centimeters at the 12 o'clock position about seven centimeters from the nipple. She had no palpable adenopathy on exam and no prior screening mammographies available for comparison at the time.

Key Points

  • Diagnostic mammogram showed extremely dense tissue and an irregular mass with speculated margins measuring 2.3 centimeters.
  • An ultrasound biopsy and MRI were performed to fully evaluate the extent of the disease.
  • The biopsy showed invasive ductal carcinoma grade 2, estrogen receptor positive 100%, progesterone receptor positive 100%, and HER2 equivocal by IHC but negative by FISH.
  • Staging with a CT scan and a nuclear medicine bone scan showed localized breast cancer with no obvious findings of metastatic disease.
  • Decisions on preoperative or neoadjuvant chemotherapy versus surgery first were based on the anatomic pathology results and the potential impact on systemic therapy recommendations.
  • Based on the ABC trials, anthracyclines may not significantly benefit hormone receptor-positive HER2-negative breast cancers with limited lymph node involvement.
  • The patient underwent surgery first, and her final pathology confirmed invasive ductal cancer, grade 3, with one out of two sentinel lymph nodes positive.
  • The RXponder study indicated that premenopausal women with node-positive disease may benefit from chemotherapy in addition to endocrine therapy.
  • Given the patient's high-risk features, adjuvant dose of Taxol and Cyclophosphamide for four cycles was recommended.

Case 2: Triple Negative Breast Cancer in the Early Setting

Summary

Our patient is a 42-year-old female presenting with a screen-detected 1.1 cm circumscribed mass in the right breast and the lower outer quadrant. The ultrasound of the breast showed a 1.6 cm hypoechoic lesion with a little bit of posterior enhancement. There were no suspicious nodes noted on either imaging modality. The patient has a family history of breast cancer in her mother and sister under age 50. The biopsy confirmed invasive ductal cancer, grade 3, triple negative.

Key Points

  • Patients with invasive triple-negative breast cancer over 5 mm are routinely offered chemotherapy, with potential escalation or de-escalation based on tumor burden and preoperative response.
  • The patient was upstaged to stage 2 based on imaging and genetic testing confirmed a BRCA1 germline mutation.
  • She was escalated to Keynote 522 chemoimmunotherapy, which includes pembrolizumab and standard chemotherapy agents.
  • Postoperative adjuvant therapy included pembrolizumab and potential incorporation of other systemic agents depending on residual disease status.
  • The CREATE-X study supports the use of adjuvant capecitabine for residual triple-negative breast cancer, and the Olympia trial supports adjuvant olaparib for BRCA mutation carriers.

Advanced Imaging and Adaptive Therapy

Summary

We are looking at ways to utilize imaging to escalate or de-escalate therapy, particularly through the design of trials like I-SPY2 and the FAIRGAIN study.

Key Points

  • I-SPY2 is a national multicenter adaptive phase two trial that looks at multiple experimental arms to estimate the efficacy of novel agents in eradicating disease during preoperative therapy.
  • Recent innovations include using MRI at various time points to predict the likelihood of a patient attaining a pathologic complete response and adapt therapy accordingly.
  • The FAIRGAIN study explored the use of FDG-PET scans to predict sensitivity to chemotherapy-free anti-HER2 therapy in HER2-positive breast cancer patients.
  • In I-SPY2, if the MRI indicates that the patient is not likely to achieve a PCR on that particular arm, they may be switched to an alternative arm in the study to see if that approach is more active in that particular subtype of breast cancer.
  • This approach helps spare the patient potentially toxic therapies that will not be beneficial and ensures access to more active agents early on in their treatment.
  • FAIRGAIN study: Patients were randomized to either standard chemotherapy with anti-HER2 treatment or anti-HER2 treatment alone, with PET scans used to predict early responders.
  • Patients predicted to respond well to anti-HER2 therapy alone had a significant reduction in chemotherapy usage, demonstrating a promising step towards personalized treatment plans.

Conclusion

Imaging plays a key role in sequencing and appropriate treatment selection for all subtypes of breast cancer. Advanced techniques and incorporation of imaging modalities can allow for more effective escalation or de-escalation of therapy in real-time. We look forward to incorporating these tools to make the best treatment decisions possible for our patients, improving outcomes while reducing toxicities and improving quality of life.

Thank you for your attention and have a good day.