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46 adult patients with non-lymphoblastic acute leukaemia (AnLL) had pretreatment proliferative activity of bone marrow (BM) blasts determined simultaneously with propidium iodide DNA flow cytofluorometry (as the percentage of cells with DNA content intermediate between the diploid and the tetraploid values, 2n-4n cell %) and in vitro tritiated thymidine cytoautoradiography (as the labelling index, LI). They were then treated with the same chemotherapy regimen, including 2-3 courses of sequential vincristine, arabinosylcytosine and adriamycin, for response induction, and monthly courses of different cytostatics for maintenance. Median 2n-4n cell % was 9.9 and median LI was 5.9. A close linear relationship (r = 0.913, p less than 0.001) between the two parameters was found. Patients having a 2n-4n cell % greater than 15.6 responded more often to chemotherapy than patients having a lower percentage (p less than 0.05) but also experienced a shorter duration of first response (p less than 0.05). Overall survival was longer in patients with 2n-4n cell % greater than 15.6 (p less than 0.02). Multiple regression analysis indicates that 2n-4n cell % is a statistically significant (p less than 0.05) independent factor correlating with duration of response in adult AnLL.

Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies.We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence.After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen.The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Flat epithelial atypia (FEA) may represent the earliest precursor of low-grade breast cancer and often coexists with more advanced atypical proliferative breast lesions such as atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN). The present study aims to investigate the association between morphological parameters of FEA and presence of malignancy at surgical excision (SE) and the clinical significance of the association of FEA with ADH and/or LIN. This study included 589 cases of stereotactic 11-gauge vacuum-assisted needle core biopsy (VANCB), reporting a diagnosis of FEA, ADH or LIN with subsequent SE from 14 pathology departments in Italy. Available slides were reviewed, with 114 (19.4 %) showing a malignant outcome at SE. Among the 190 cases of pure FEA, no statistically significant association emerged between clinical–pathological parameters of FEA and risk of malignancy. Logistic regression analyses showed an increased risk of malignancy according to the extension of ADH among the 275 cases of FEA associated with ADH (p = 0.004) and among the 34 cases of FEA associated with ADH and LIN (p = 0.02). In the whole series, a statistically significant increased malignancy risk emerged according to mammographic R1–R3/R4–R5 categories (OR = 1.56; p = 0.04), extension (OR = 1.24; p = 0.04) and grade (OR = 1.94; p = 0.004) of cytological atypia of FEA. The presence of ADH was associated with an increased malignancy risk (OR = 2.85; p < 0.0001). Our data confirm the frequent association of FEA with ADH and/or LIN. A diagnosis of pure FEA on VANCB carries a 9.5 % risk of concurrent malignancy and thus warrants follow-up excision because none of the clinical–pathological parameters predicts which cases will present carcinoma on SE.

Percutaneous core biopsy (CB) has been introduced to increase the ability of accurately diagnosing breast malignancies without the need of resorting to surgery. Compared to conventional automated 14 gauge needle core biopsy (NCB), vacuum-assisted needle core biopsy (VANCB) allows obtaining larger specimens and has recognized advantages particularly when the radiological pattern is represented by microcalcifications. Regardless of technical improvements, a small percentage of percutaneous CBs performed to detect breast lesions are still classified, according to European and UK guidelines, in the borderline B3 category, including a group of heterogeneous lesions with uncertain malignant potential. We aimed to assess the prevalence and positive predictive values (PPV) on surgical excision (SE) of B3 category (overall and by sub-categories) in a large series of non-palpable breast lesions assessed through VANCB, also comparison with published data on CB. Overall, 26,165 consecutive stereotactic VANCB were identified in 22 Italian centres: 3107 (11.9%) were classified as B3, of which 1644 (54.2%) proceeded to SE to establish a definitive histological diagnosis of breast pathology. Due to a high proportion of microcalcifications as main radiological pattern, the overall PPV was 21.2% (range 10.6%-27.3% for different B3 subtypes), somewhat lower than the average value (24.5%) from published studies (range 9.9%-35.1%). Our study, to date the largest series of B3 with definitive histological assessment on SE, suggests that B3 lesions should be referred for SE even if VANCB is more accurate than NCB in the diagnostic process of non-palpable, sonographically invisible breast lesions.

Of 836 nonpalpable breast lesions histologically assessed between 1985 and 1991 at the Milan Cancer Institute, 427 were malignant (51%). Microcalcifications were present in 283 tumors (66%), alone in 200 cases or associated with a mass (72 cases) or within a focal distortion (11 cases). Several mammographic, clinical and histological features were analyzed, comparing the 283 lesions with microcalcifications with the 144 tumors represented only by nodular opacities or distortions. This was done to assess the existence of morphologic and prognostic characters differentiating the two subsets and to investigate the reliability of mammography in estimating lesion size. On the average, in our series of cases, the patients with microcalcifications were younger, had a higher rate of dense breasts and a large number of partially or totally intraductal carcinomas. In situ carcinomas were frequent and minimal lesions (5 mm) accounted for 43% of the whole at pathologic examination. However, the lesions with microcalcifications were associated with more positive nodes (32% vs 18%). Therefore, microcalcifications, although generally representing an early sign of cancer, appear to suggest a less favorable prognosis.