Radiation is an Important Component of Therapy for Patients with Stage III Breast Cancer Who Achieve a Pathological Complete Response after Neoadjuvant Chemotherapy

Reviewer: Voika BarAd, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 18, 2005

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Presenter: SE McGuire
Presenter's Affiliation: Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX
Type of Session: Scientific

Background

Neoadjuvant chemotherapy is the standard for locally advanced breast cancer and for large operable breast cancer.  A pathological complete response rate of 15-20% after neoadjuvant chemotherapy is reported in most series.  Breast cancer patients who achieve a pathological complete response after neoadjuvant chemotherapy have been reported to have an excellent outcome.  The optimal local treatment for these patients is not well defined.  Despite their favorable prognosis, 10-20% of patients with a pathological complete response after neoadjuvant chemotherapy will experience a recurrentce of breast cancer.  The study investigates the value of radiation therapy in a large cohort of breast cancer patients who achieve pathological complete response after neoadjuvant chemotherapy.

Materials and Methods

  • 1451 patients with non-metastatic breast cancer were treated with neoadjuvant chemotherapy; the 226 (16%) who achieved pathological complete response (defined as no residual invasive disease in both the breast and the lymph nodes) were reviewed retrospectively.
  • The clinical stage (AJCC 2003) at diagnosis was stage I-II in 37% of patients and stage III in 52% of patients.
  • 11% of patients had breast inflammatory disease.
  • Breast conservative surgery was performed in 40% of cases and mastectomy was performed in 58%, with a remaining of 2% of patients receiving only axillary dissection.
  • The chemotherapy was anthracycline-based in 92% of patients with 42% also receiving taxanes; the median number of chemotherapy cycles was 4.
  • Radiotherapy was used in 87% of patients; all patients with breast inflammatory disease received radiotherapy.
  • The patients treated with radiotherapy had more commonly stage III disease compared with those who did not receive irradiation (55% vs 19%).
  • Median follow up was 63 months.

Results

  • 10 years actuarial rate of developing any recurrence (distant or local recurrence) was 16%.
  • The group receiving radiotherapy demonstrated a trend toward increase in cause-specific survival, despite having a greater percentage of patients with more advanced disease at presentation.
  • The overall cause-specific-survival was 88% for the radiation group vs 68% in the no radiation group.
  • A subset analysis revealed that the majority of the survival difference was captured by non-inflammatory stage III disease; in this group the radiation use was associated with a significant lower rate of development of distant metastasis and an improved cause-specific survival and overall survival.
  • For stage I-II disease, 10 years rate of freedom from local regional recurrence for the radiation group was 100% compared to 95% for no radiation group.
  • For stage III disease, 10 years rate of freedom from local regional recurrence for the radiation group was 91% compared to 66% for no radiation group.

Author's Conclusions

  • Although breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy have a favorable prognosis, a subset of these patients will experience recurrence of their disease.
  • The patients with stage III disease, who achieved pathological complete response after neoadjuvant chemotherapy and receive adjuvant irradiation after surgery, have a significant lower rate of locoregional and distant recurrences than those who did not receive radiation therapy. The benefit was also associated with an improved cause-specific and overall survival.
  • Therefore, all patients with stage III breast cancer who achieve pathological complete response after neoadjuvant chemotherapy should receive radiation as a component of their care.

Clinical/Scientific Implications

Increased breast health awareness has led to earlier stage distribution among breast cancer patients in the United States.  However, locally advanced tumors remain a major source of morbidity and mortality. Early attempts to control this high-risk pattern of disease with surgery and radiation alone had disappointingly high rates of treatment failure in locoregional and metastatic sites. Multimodality strategies represent a major step forward in the management of these difficult cancers.  Studies have shown that after neoadjuvant chemotherapy and surgery, comprehensive radiation benefits both local control and survival for patient with clinical stage III breast cancer.  Radiation should be considered for these patients regardless of their response to initial chemotherapy.  Ongoing investigations of locally advanced breast cancer include a trial trying to define the optimal extent of locoregional irradiation in patients who experienced a strong response to neoadjuvant treatment.