Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

The learning curve for sentinel node biopsy in breast cancer: practical considerations.

HYPOTHESIS: Performance of sentinel node biopsy (SNB) instead of full axillary lymph node dissection (ALND) by inexperienced surgeons will lead to understaging of some women with breast cancer and increased costs. DESIGN: A decision analysis model was used to investigate the implications of SNB vs. full ALND during the learning phase (60-80 procedures). This model simulates a randomized trial of 10000 women in each arm. Data regarding the learning curve were obtained from published series. MAIN OUTCOME MEASURES: Percentage of women with inaccurate staging of their breast cancer, overall survival, quality-adjusted survival, and potential costs of SNB vs ALND. RESULTS: Performance of SNB instead of ALND results in inability to locate a sentinel node in 38% of attempts during the learning phase (compared with 10% in later cases) and understaging in 12% of patients during the learning phase (compared with 0% in later cases). This understaging is associated with a small decrement in survival (1%-2%) and an increased risk of axillary recurrence. Sentinel node biopsy is cost-effective only when the ability to detect sentinel nodes exceeds 80%; and the cost of SNB is less than 50% of the cost of ALND. CONCLUSIONS: To ensure accurate staging of patients with breast cancer, all surgeons should perform full ALND while learning SNB techniques. Only after documentation of accuracy of SNB (sensitivity >90%) should full ALND be omitted for women with negative sentinel nodes.

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18.

PURPOSE: To determine whether preoperative doxorubicin and cyclophosphamide (AC) permits more lumpectomies to be performed and decreases the incidence of positive nodes in women with primary breast cancer. PATIENTS AND METHODS: Women (n = 1,523) were randomized to National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18; 759 eligible patients received postoperative AC and 747, preoperative AC. The clinical size of breast and axillary tumors was determined before each of four cycles of AC and before surgery. Tumor response to preoperative therapy was clinically complete (cCR), partial (cPR), stable (cSD), or progressive disease (cPD). Tissue from patients with a cCR was evaluated for a pathologic complete response (pCR). RESULTS: Breast tumor size was reduced in 80% of patients after preoperative therapy; 36% had a cCR. Tumor size and clinical nodal status were independent predictors of cCR. Twenty-six percent of women with a cCR had a pCR. Clinical nodal response occurred in 89% of node-positive patients: 73% had a cCR and 44% of those had a pCR. There was a 37% increase in the incidence of pathologically negative nodes. Before randomization, lumpectomy was proposed for 86% of women with tumors < or = 2 cm, 70% with tumors 2.1 to 5.0 cm, and 3% with tumors > or = 5.1 cm. Clinical tumor size and nodal status influenced the physician's decision. Overall, 12% more lumpectomies were performed in the preoperative group; in women with tumors > or = 5.1 cm, there was a 175% increase. CONCLUSION: Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes. The greatest increase in lumpectomy after preoperative therapy occurred in women with tumors > or = 5 cm, since women with tumors less than 5 cm were already lumpectomy candidates. Preoperative therapy should be considered for the initial management of breast tumors judged too large for lumpectomy.

Definitive breast cancer surgery as an outpatient: a rational basis for the transition.

The transition of definitive breast cancer surgery to an outpatient setting cannot be done without some major philosophical and technical changes on the part of the surgeon. This paper outlines the changes in the author's practice made over two decades demonstrating that this transition has had no effect on outcome. Definitive surgical care for breast cancer can occur in a cost-effective fashion totally on an outpatient basis.

Rigid fixation of facial fractures in children.

This article presents a retrospective analysis of a selective use of rigid fixation among 62 children with facial fractures, treated at a Level I trauma center over a 5-year period (1986-1991). There were 21 mandible fractures, 11 orbital fractures, 11 zygomaticomalar complex fractures, 7 nasal fractures, 5 maxillary fractures, 3 pan-facial fractures, 2 nasal-orbital-ethmoidal complex fractures, and 2 frontal sinus fractures. Only 18 children had rigid fixation of their injuries. Complications of Le Fort upper facial fractures repaired with rigid fixation involved perioperative sinusitis; one case required oral antibiotics, the other ethmoidectomy and maxillary antrostomy. One child with a Le Fort fracture had delayed exposure of a zygomaticomalar buttress plate, which required surgical removal. Permanent enophthalmos occurred in two children with Le Fort fractures. The authors conclude that traditional conservative management is appropriate in most cases. However, in children aged 13 and older with mandible fractures and children with complex mid- and upper facial fractures, a judicious use of rigid fixation has advantages over the traditional techniques.

A late defect in wound healing associated with recurrent spontaneous pneumothoraces: a presumptive role for abnormal collagenase activity.

This case report concerns an individual with a defect in wound healing which resulted in recurring, bilateral pneumothoraces during the late postoperative period. This patient had no history of systemic disease or wound healing abnormalities before his recurrent wound disruption. Physical examination and routine biochemical studies failed to identify any causative agent for the multiple wound dehiscences in the patient. Histologic examination of scar tissue showed collagen fiber bundles with a diameter 50% less than that of normal fibrils. Elastic fibers were barely visible, and the scar tissue included a large number of inflammatory cells. A significant finding was an elevated and aberrant expression of collagenase by a fibroblast cell line established from a skin biopsy specimen. This enhanced level of collagenase expression could be inhibited by treatment of the cells with diphenylhydantoin, an inhibitor of collagenase biosynthesis. After initiation of diphenylhydantoin therapy, the patient's scar formation normalized with the recurrent pneumothoraces. These findings support the conclusion that an abnormal expression of collagenase resulted in enhanced degradation of collagen in the patient's wounds, thereby leading to wound dehiscence.

Subungual exostosis of the fingers.

Subungual exostosis in the digit is an uncommon benign tumor. Only 21 (10%) of 203 cases reported in the literature occurred in the hand. We present a recent case, detailing diagnosis, pathologic findings, and management.

The external rhinoplasty approach for rhinologic surgery in children.

The external rhinoplasty is a versatile approach for exposing nasal anatomy in children and has been utilized for a variety of rhinologic problems (N = 35). These have included septal deviation (11), cleft lip nasal deformity (10), unilateral choanal atresia (five), nasal dermoids (four), and problems of the sphenoidal sinus (five). For children with septal deformities, the external approach allows complete intranasal visualization, providing access for careful and conservative reconstruction. In children with cleft lip nasal deformity, decortication allows for direct sculpting of the alar cartilages. For unilateral choanal atresia, the external technique provides exposure of the posterior vomer as in the transpalatal approach, but without the risk to palatal growth. For nasal dermoids, the open rhinoplasty offers wider exposure with more control over the medial osteotomies, a better view of the cribriform plate, and enhanced cosmesis. For problems of the sphenoid, the external route utilizes the guiding midline intranasal structures for rapid and direct entry into the sinus. In our study, the age range of the children was between 7 months and 18 years. The range of follow-up was between 6 months and 5 years. The techniques for the individual procedures are described, along with a rationale for their employment. There were no postoperative complications, and no long-term problems associated with the use of the external technique. In conclusion, the enhanced exposure provided by the external rhinoplasty approach in children facilitates rhinologic procedures on the soft tissues of the nose and the nasal architecture, as well as in the central core of the face.

Reduction mammaplasty: cosmetic or reconstructive procedure?

Ninety-two of 220 plastic surgeons submitted information from 600 women (the last 15 to 20 reduction mammaplasties by each surgeon) regarding height, weight, and amount of breast tissue removed. In a second survey to estimate percentages of women who sought reduction mammaplasties for purely cosmetic reasons, for mixed reasons, and for purely medical reasons, 132 of the same 220 surgeons responded. All women whose removed breast weight was less than the 5th percentile sought the procedure for purely cosmetic reasons, and all women whose breast weight was greater than the 22nd percentile sought the procedure for medical reasons. Those women whose removed breast tissue weight was between the 5th and the 22nd percentiles had mixed reasons for requesting the procedure.

Influence of estrogen receptors on survival and recurrence in patients with breast cancer without lymph node metastases.

A retrospective chart review was conducted to determine the prognostic effect of estrogen receptor (ER) protein in patients with node-negative operable breast cancer. One hundred nine patients with breast cancer whose tumors underwent ER analysis and whose lymph node negativity was established histologically were studied. Based on life-table analysis, the overall survival at six years was 92.7% for ER-positive patients, 95.3% for ER-negative patients, and 94.4% for ER-borderline patients. The disease-free survival was 83.3%, 92.8%, and 71.4%, respectively. Survival and disease-free survival were also correlated to menopausal status. The difference in survival was not statistically significant at six years. We conclude that in node-negative primary operable breast cancer, ER status should not be used as a discriminant for adjuvant treatment.

Early breast cancer detected by mammography. Marshfield Clinic experience.

Use of mammography in asymptomatic women does discover breast cancer at an earlier point in development, as measured by size, invasiveness, and nodal involvement. The integration of mammography into routine periodic evaluation of asymptomatic women over 35 years of age should diminish the threat of breast cancer.