Background: Despite recent advances in combined multimodality treatments, locally advanced breast carcinoma continues to carry a poor prognosis. We conducted a phase I/II study to evaluate the pathological response rates after a novel neoadjuvant combination treatment. Various thermal parameters were analyzed for their impact on pathologic response.

Methods: Eligible patients received four cycles of neoadjuvant liposomal doxorubicin, paclitaxel, and hyperthermia. They subsequently underwent either a modified radical mastectomy or lumpectomy with axillary node dissection followed by radiation therapy and then eight cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy.

Results: Forty-seven patients with stage IIB-III locally advanced breast cancer were enrolled. 15/47 (32%) had inflammatory breast cancer. Complete pathologic response was defined as no evidence of invasive carcinoma in the surgical specimen. Partial pathologic response was defined as a reduction in tumor size by at least 50% of initial size estimates based on radiographic studies. Of the 43 evaluable patients, 4 patients (9%) achieved a pathologic complete response. The total pathologic response rate (complete + partial) was 60%. The mean T90 and T50 for responders were 39.8°C and 41.1°C, respectively. For non-responders, they were 39.4°C and 40.7°C, respectively. There was a trend for greater cumulative equivalent minutes (CEM) at 43°C T50 between responders and non-responders (median 46.3 vs. 42.0, p=0.23, Mann-Whitney rank sum test). The CEM 43 T90 was statistically greater for those with a pathologic response (median 13.2 vs. 8.9, p=0.048, Mann-Whitney rank sum test).

Conclusions: The CEM 43 is an important thermal parameter for achieving a pathologic response with the novel neoadjuvant combination of liposomal doxorubicin, paclitaxel, and hyperthermia in locally advanced breast cancer. A greater CEM 43 T90 was significantly correlated with attaining this pathologic response.