Multicentric/multifocal breast cancer with a single histotype: is the biological characterization of all individual foci justified?

BACKGROUND: Invasive multiple breast cancers with a single histological feature (MBCSH) are routinely assessed for biological parameters to indicate adjuvant treatments only in the largest invasive carcinomas. However, the heterogeneity of individual foci in multiple carcinomas has not been widely studied. We analyzed whether such biological features are differently expressed in different MBCSH foci. PATIENT AND METHODS: One hundred and thirteen invasive MBCSH were tested over a 5-year period. The expression of estrogen (ER) and progesterone (PgR) receptors, Ki-67 proliferative index, expression of HER2 and tumor grading were prospectively determined in each tumor focus, and mismatches among foci were recorded. RESULTS: Mismatches in ER status were present in 5 (4.4%) cases and PgR in 18 (15.9%) cases. Mismatches in tumor grading were present in 21 cases (18.6%), proliferative index (Ki-67) in 17 (15%) cases and HER2 status in 11 (9.7%) cases. CONCLUSIONS: In our experience, invasive MBCSH showed heterogeneity among foci. In our clinical practice, such assessment led to 14 (12.4%) patients receiving different adjuvant treatments compared with what would have been indicated if we had only taken into account the biologic status of the primary tumor.

Atypical ductal hyperplasia of the breast: the controversial management of a borderline lesion: experience of 47 cases diagnosed at vacuum-assisted biopsy.

The present paper describes our experience of 47 cases of atypical ductal hyperplasia (ADH) diagnosed at vacuum-assisted biopsy. From June 1999 to December 2003, 47 consecutive diagnoses of non-palpable ADH of the breast were made by 11-gauge vacuum-assisted biopsy (Mammotome). Of these, 17 were subjected to surgical excision and 11 underwent a second Mammotome at the site of the previous vacuum-assisted biopsy. Diagnostic underestimation occurred in only two cases, with a surgical diagnosis of ductal carcinoma in situ. In both patients, aged between 46 and 55 years, the radiological images showed microcalcifications of >20 mm, and the lesions were not completely removed by Mammotome. Despite the obvious limitations of the present study, it can be concluded that the probability of underestimating ADH diagnosis by Mammotome appears to be related to the radiological features of the lesion (>20 mm) and to the adequacy of specimens.

Performance indicators of organized cervical screening in Romagna (Italy).

The availability of published data from organized cervical screening programmes in southern Europe is scant. In the Italian area of Romagna, a first round of organized screening (based on a 3-yearly Pap smear for women aged 25-64 years) was initiated between December 1995 and January 1997 and was completed in an average of 42 months (range 36-48 months). The target population included 305 478 women. Of these, 253 949 were eligible and received a personal letter of invitation. Age-specific screening performance indicators were calculated according to standard methods. The response rate within 6 months of invitation was 49.1% (n=124 621). The total participation rate including women who presented later was 61.7% (n=156 735). The recall rate was 35.2 per 1000 of participants (n=5514). Positive cytology results were distributed as follows: atypical squamous cells of un-determined significance/atypical glandular cells of undetermined significance (ASCUS/AGUS) 40.1%, low-grade squamous intraepithelial neoplasia (LGSIL) 48.6%, high-grade squamous intraepithelial neoplasia (HGSIL) 10.7% and carcinoma 0.7%. Compliance to colposcopy follow-up was 93.4% (n=5149). The biopsy rate was 52.4% (n=2696) of patients undergoing colposcopy. The detection rate was 4.5 per 1000 of participants (n=707) for CIN2-3 and 0.5 (n=75) for invasive carcinoma. The proportion of microinvasive carcinomas was 36.0% (n=27). The positive predictive value for CIN2-3/carcinoma was 5.8% for the cytology reports of ASCUS/AGUS, 7.6% for those of LGSIL, 76.5% for those of HGSIL, and 100.0% for those of carcinoma (80.4% for combined HGSIL/carcinoma). The ratio of observed to expected (or prevalent to incident) cases of invasive carcinoma was 2.35 (95% confidence interval (CI) 1.85-2.95). In conclusion, most early results of the programme were compatible with an acceptable performance.

Schedule-dependent interaction of doxorubicin, paclitaxel and gemcitabine in human breast cancer cell lines.

We showed previously that a sequential treatment with doxorubicin (4 hr) followed by paclitaxel (24 hr) (Dox-->Pacl) induces a synergistic cytotoxic effect in the BRC-230 breast cancer cell line and in human primary breast cancer cultures. The validity of this experimental finding was confirmed in a clinical phase I/II study on advanced breast cancer patients. To improve the cytotoxic effect obtained by the Dox-->Pacl sequence, we analyzed the effect of adding gemcitabine (Gem) to the Dox-->Pacl sequence in a preclinical study. Our study was performed on BRC-230 and MCF-7 cell lines, and cytotoxic activity was evaluated by the sulforhodamine B assay and the type of drug interaction by Drewinko's test. When Gem (0.01 microg/ml for 24 hr) was given immediately or 24 hr after Dox-->Pacl, an antagonistic cytotoxic effect was observed. Conversely, a synergistic effect was found when Gem was given 48 hr after Dox-->Pacl. From results of flow cytometric analysis, the synergistic effect was attributed to cell cycle perturbation. Cells were arrested in G2-M (95% in treated vs. 21% in control samples) 24 hr after Dox-->Pacl treatment. The block progressively recovered thereafter, and after a further 24 hr, at the time of Gem treatment, the cells progressed into the G1-S phase boundary (the cell cycle phase susceptible to the cytocidal effect of the drug). Our findings suggest that the interactions of Dox, Pacl and Gem are highly schedule- and time-dependent and should be taken into consideration in the planning of clinical protocols.

A Phase I/II study of paclitaxel and doxorubicin in the treatment of advanced breast cancer.

We designed a clinical study in which fixed doses of doxorubicin were infused by intravenous bolus 16 hours before escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, princeton, NJ) for the treatment of patients with advanced breast cancer, an interval selected to allow systemic clearance of doxorubicin before administration of paclitaxel in an outpatient setting. Courses of fixed-dose doxorubicin 50 mg/m2 by intravenous bolus and paclitaxel (doses escalated from 130 mg/m2 to 250 mg/m2 via dose escalation of 30 mg/m2) were repeated every 21 days, to a maximum of eight cycles. Maximum tolerated dose was reached if two or more of six patients at a given dose level were affected by the following events: absolute neutrophil count less than 500/microliter for > or = 7 days, absolute neutrophil count less than 100/microliter for > or = 3 days, insufficient hematopoietic recovery with absolute neutrophil count less than 1,500/microliter on day 21, febrile neutropenia, grade 4 thrombocytopenia, any World Health Organization grade 3 nonhematologic toxicity for more than 7 days. There were 19 patients enrolled; the patients received a total of 128 treatment courses. Grade 4 neutropenia was the main side effect, occurring in 20% of courses but generally not associated with clinical events. No relevant clinical cardiac toxicity or alteration of left ventricular ejection fraction was observed. Other toxicities included complete alopecia, mild peripheral neuropathy, and mild myalgia. There was a reduction of one dose level for moderate myalgia in one patient (190 mg/m2 level). Complete alopecia was always present. Maximum tolerated dose was not reached at paclitaxel 250 mg/m2. Ultimately, the introduction of this combination in the adjuvant setting is warranted.

Intraductal papillomas: diagnostic and surgical procedures.

A series of 98 patients with spontaneous nipple discharge, is reported. Diagnosis was based on: clinical examination, cytology of breast secretion, mammography and galactography. Surgical resection was recommended in the following cases: galactographic evidence of intraductal papilloma or papillomatosis, dubious or positive cytology, persisting hemorrhagic or sero-hemorrhagic secretion. The injection of vital staining before the operation allowed the precise location of the lesion. In the group of patients studied ten cases of ductal carcinomas (5 in situ and 5 smaller than 1 cm), 4 cases of atypical intraductal hyperplasia, 13 cases of solitary papilloma and 22 cases of multiple papillomatosis were diagnosed.

A retrospective study of FAM regimen in 38 patients with advanced gastric cancer.

Gastric carcinoma has a very poor prognosis, with a survival rate at 5 years of 13%. Various chemotherapy regimens have been used in the advanced stages of the disease. The best results were obtained using the FAM combination. We treated 38 patients with advanced measurable gastric cancer using the FAM combination and obtained 23.67% complete plus partial remission (CR + PR) (32% with more restrictive criteria for eligible patients) and 34% no change. The median length of response was 30 weeks in CR patients (range 20-100) and 26 weeks (range 12-34) in PR patients. Responsive patients (CR + PR) had a median survival of 12.3 months (range 5-22) compared to nearly 4 months (range 2-8) for unresponsive patients.