Predictors of pathologic response and correlation with long-term outcomes in a trial of neoadjuvant concurrent paclitaxel radiation in locally advanced breast cancer (LABC).

Abstract

589 Background: The association of hormone receptor (HR) status of the original tumor with pathologic response and correlation with DFS and OS from a multi-institutional trial of concurrent paclitaxel (P) and radiation (RT) are reported. Methods: 105 LABC patients were treated with neoadjuvant concurrent P and RT (P: 30 mg/m2 2x/week for 10-12 weeks; RT: 1.8 Gy daily to breast, axillary and supraclavicular LN weeks 2-7 to total of 45 Gy followed by a tumor boost of 14 Gy at 2 Gy/fraction). Pathologic response was defined as absence of invasive cancer in breast and LN (pCR) or persistence of less than 10 microscopic foci of invasive cancer in breast or LN (pPR). Logistic regression methods were used to predict response status, logrank tests and Cox proportional hazards methods to evaluate DFS and OS in relation to HR status and pathologic response. Results: Pathologic response (pCR+pPR) for the entire cohort was achieved in 36/105 patients (34%, 95% CI: 25-44%). For all patients, lack of a pathologic response conveyed 4.4 times greater death rate than for pathologic responders (95% CI 1.5-12.7). Nonresponders have a median survival time of 84 months; median not reached for responders. A significantly greater rate of pathologic response occurred in patients with HR negative cancers compared with HR positive cancers (p < 0.001): 54% (95% CI 39-69%) compared to 18% (95% CI of 9-30%). HR status was the only predictor of pathologic response after concurrent P-RT. As expected, HR negative tumors had a worse prognosis than HR positive ones; this feature remained despite the achievement of a pathologic response. However, pathologic response and HR status jointly predicted DFS (likelihood ratio p < 0.001). The clinical benefit from achieving a pathologic response was most pronounced in patients with HR negative tumors with a reduction in recurrence or death rate of 75% as compared with HR negative nonresponders. Conclusions: Conclusions: HR status is highly predictive of response to neoadjuvant concurrent paclitaxel and radiation; more than half of the patients with HR negative tumors achieved a pathologic response, which translates into superior DFS and OS. No significant financial relationships to disclose.