F. C. Ames

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy

One hundred seventy‐four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5‐fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease‐free after induction chemotherapy and local treatment. The median follow‐up of this group of patients is 59 months. The 5‐year disease‐free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5‐year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor‐positive tumors, had a trend for better survival than older patients and those with estrogen receptor‐negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty‐six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease‐free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.

Breast Conservation After Neoadjuvant Chemotherapy: The M.D. Anderson Cancer Center Experience

PURPOSE To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. PATIENTS AND METHODS Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. RESULTS At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1-2 v T3-4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P =.19). CONCLUSION Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.

Accuracy of Physical Examination, Ultrasonography, and Mammography in Predicting Residual Pathologic Tumor Size in Patients Treated With Neoadjuvant Chemotherapy

Objective:To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy. Background:Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting. Methods:We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic. Results:Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of ±1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24–0.35) indicated poor agreement between clinical and pathologic measurements. Conclusion:Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy.

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma

Two hundred and seventy‐four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48‐hour (79 patients) or 96‐hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinial cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48‐hour or 96‐hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P < 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P < 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a >75% decrease in the frequency of clinical congestive heart failure at cumulative dosages ≥ 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48‐hour or 96‐hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus.

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5‐fluorouracil, and cisplatin (EFP). Ninety‐eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow‐up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP‐induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

The role of limited surgery with irradiation in primary treatment of ductal in situ breast cancer

The results of management of ductal carcinoma in situ with limited surgery and radiotherapy are presented at a median follow-up of 92 months. In 44 treated breasts the actuarial 10-year loco-regional control rate was 91%, four patients having recurred. Each loco-regional failure was due to invasive carcinoma and three of the affected patients have developed metastases. No patient developed metastases without previous clinically-evident invasive loco-regional disease. The 10-year disease-specific survival rate was 96%. Previous publications have shown that the 25% or greater risk of local failure after limited excision of ductal carcinoma in situ can be reduced by irradiation of the breast. Our results demonstrate that good loco-regional control is maintained in the longer term.

LOCALLY ADVANCED NONINFLAMMATORY BREAST CANCER

Treatment of locally advanced noninflammatory breast cancer has changed markedly over the past 50 years. Haagensens description of the clinical signs that define inoperable and operable tumors was the first realization that radical surgery alone could not cure the majority of women with locally advanced disease. Studies of the use of local therapy alone (surgery or radiation therapy) confirmed that most patients developed both distant metastatic disease and a high rate of local-regional failure. Combination surgery and radiation therapy regimens improved local control but did not influence long-term survival. The advent of successful multimodal regimens incorporating systemic treatment (chemotherapy or chemohormonal therapy) as well as local therapy (surgery and radiation) has significantly improved disease-free and overall survival as well as local-regional control. The benefits of neoadjuvant and adjuvant chemotherapy regimens have been debated. Neoadjuvant therapy allows clinical and pathologic assessment of tumor response to the chemotherapy regimen. In addition, local-regional control seems to be improved, and reductions in the size of the primary tumor allow breast-preserving procedures, even in patients initially not believed to be candidates for resection. Longer follow-up of these conservatively treated patients will be needed, however, to determine whether local-regional control is preserved.

Economic impact of reducing hospitalization for mastectomy patients

In 1985, two policies designed to reduce hospitalization charges for mastectomy patients were instituted at the M.D. Anderson Cancer Center at Houston. The first was a policy of “same-day” admissions for elective surgery patients, and the second was early postoperative discharge for mastectomy patients with suction catheter drains in place. The economic savings resulting from these policies was analyzed by comparing demographics, operation, stage of disease, hospital stay, hospital charges, and complications for two groups of patients. Fifty-nine consecutive mastectomy patients treated between 1983 and 1984, before these policy changes, had “standard management” consisting of hospital admission 24 hours before surgery and discharge only after the surgical drains were removed. Sixty-one consecutive mastectomy patients treated between 1986 and 1987, after these policy changes went into effect, were admitted from the recovery room after surgery and were discharged with drainage catheters in place, usually within 72 hours. All operations were performed by the same faculty surgeon as a representative experience of the General Surgery faculty. The average hospital stay was reduced from 10.5 to 4.3 days. A mean 39% reduction in hospital charges (from

Adjuvant therapy with escalating doses of doxorubicin and cyclophosphamide with or without leukocyte alpha-interferon for stage II or III breast cancer.

4867.00 to

Primary chemotherapy for breast cancer : response to preoperative chemotherapy as prognostic factor

2981.00) was achieved by instituting the policies of “same-day” admission and early postoperative discharge with drainage catheters in place. Complication rates were not changed. Implementation of this policy resulted in an estimated savings of