Barbara D. Florentine

Preoperative Twice-Weekly Paclitaxel With Concurrent Radiation Therapy Followed by Surgery and Postoperative Doxorubicin-Based Chemotherapy in Locally Advanced Breast Cancer: A Phase I/II Trial

PURPOSE Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy. PATIENTS AND METHODS Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m(2) delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. RESULTS Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer). CONCLUSION Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC.

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-Fluorouracil and radiation therapy

PURPOSE/OBJECTIVE 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

The reliability of fine-needle aspiration biopsy as the initial diagnostic procedure for palpable masses: a 4-year experience of 730 patients from a community hospital-based outpatient aspiration biopsy clinic.

Fine‐needle aspiration biopsy (FNAB) is a reliable, rapid, minimally invasive alternative to surgical biopsy when it is performed by physician specialists for the diagnosis of palpable masses. FNAB may be under‐utilized in community hospitals in the U.S. because physicians without specialty training commonly provide the service, resulting in less reliable results.

Core needle biopsy

Fine‐needle aspiration (FNA) biopsy is an established, highly accurate method for diagnosing palpable breast lesions. However, in some cases a definitive diagnosis cannot be made by FNA alone, either due to the inherent limitations of cytology itself or the ability to obtain adequate material for diagnosis. This study evaluated the usefulness of a supplemental core needle biopsy performed by a cytopathologist in conjunction with an FNA biopsy in select patients.

Preoperative 5-fluorouracil and radiation therapy for locally advanced breast cancer

BACKGROUND Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability. METHODS Eligible patients had locally advanced breast cancer deemed unresectable with primary wound closure. Patients received 8 weeks of infusional 5-fluorouracil (5-FU) 200 mg/m2 per day and radiation therapy to 50 Gy. Patients rendered resectable underwent modified radical mastectomy (MRM) followed up by chemotherapy. RESULTS Of 30 evaluable patients, 73% had an objective clinical response. All were able to undergo MRM with primary wound closure; 63% had residual disease, 20% had minimal microscopic disease, and 17% had complete pathologic response. Treatment-related toxicity was minimal. Surgical morbidity was not increased. CONCLUSIONS Infusional 5-FU with concomitant radiotherapy is well tolerated and effective at producing shrinkage in the majority of patients, converting inoperable breast cancer to easily resectable disease.

Detection of hyperdiploid malignant cells in body cavity effusions by fluorescence in Situ hybridization on thinPrep slides

Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology.

Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report.

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine‐needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor. Diagn. Cytopathol. 23:46–50, 2000.

Linkage analysis and loss of heterozygosity for chromosome arm 1p in familial breast cancer

We conducted linkage analysis of 64 multiple‐case families with early‐onset bilateral breast cancer using DNA markers on chromosome band 1p36. Evidence against tight linkage was obtained using a dominant model for transmission (summary LOD scores at recombination fraction θ = 0.000001 were ‐4.71 for D1S160 and ‐2.70 for D1S170). Similar results were obtained after excluding 20 families that were potentially attributable to BRCA1 or BRCA2. We also investigated loss of heterozygosity for a panel of markers on chromosome arm 1p using breast tumors from affected family members. The most common regions of allele loss were 1p36 (32% for D1S160, 35% for D1S243) and 1p32 (51% for MYCL). The frequency and location of 1p allele loss did not differ substantially from previous studies of sporadic breast cancer. We conclude that 1p36 probably does not contain a locus of susceptibility for a large proportion of breast cancer families, but a variety of loci on 1p may contribute to progression of familial and sporadic disease. Genes Chromosomes Cancer 25:354–361, 1999.

Conservative Excision of Wire‐Bracketed Breast Carcinomas: A Community Hospital's Experience

Abstract:  We report our experience with excision of hooked‐wire bracketed breast carcinomas in a community hospital setting. The mammographic and pathology reports from 36 nonpalpable or minimally palpable breast cancers were retrieved from a single surgical oncologists office records and a number of factors that might influence a successful initial surgical excision were examined. The median lesion size was 1 cm. The radiographic abnormalities were microcalcifications only in 14 cases (39%), combined mass/density and microcalcifications in 9 cases (25%), and mass/density without microcalcifications in 13 cases (36%). The median number of bracketing wires placed was two. A prior fine‐needle aspiration (FNA) or core biopsy was performed in 29 of the 36 cases (81%). Of these, 27 were positive for malignancy. The tumor was considered to be inadequately excised if it was present within 5 mm of any surgical margin; this outcome occurred in 21 of the 36 cases (58%). Fifteen cases (42%) had tumor involving either the margin or extending to within 1 mm of the margin. Inadequately excised lesions were more commonly seen with increasing tumor size, a radiographic appearance of microcalcifications without an associated mass, and a pathologic diagnosis of ductal carcinoma in situ (DCIS). An intraoperative consult led to taking additional marginal tissue in 23 cases and was successful in achieving final clear histologic margins in 8 of these (35%). Our experience suggests that there are at least two ways to optimize the adequacy of conservative excision of nonpalpable or difficult‐to‐palpate breast cancers using standard modalities presently available in most community hospitals. These are (a) having the pathologist and radiologist available for intraoperative consultation and (b) obtaining a tissue diagnosis of malignancy preoperatively. The use of bracketing wires to better delineate the margins of tissue to be excised may also be helpful, but this needs to be further evaluated in a randomized study. 

Xanthogranulomatous cystitis as a cause of elevated carcinoembryonic antigen mimicking recurrent colorectal cancer: Report of a case

We report a case of xanthogranulomatous cystitis that developed in a patient with a history of colon cancer. While undergoing adjuvant chemotherapy with fluorouracil and levamisole, rising carcinoembryonic antigen (CEA) levels and the appearance of a pelvic mass, suspicious for recurrent cancer, were identified. Exploratory laparotomy demonstrated the presence of a benign condition of the bladder, xanthogranulomatous cystitis, which was resected by partial cystectomy. CEA levels have normalized. This is the first reported case of xanthogranulomatous cystitis producing an elevated CEA level.