Proteus Donna is a randomised controlled trial aimed at prospectively evaluating screening with digital breast tomosynthesis (DBT), including interval cancer detection (ICD) and cancer detection (CD) in the analysis as a cumulative measure over subsequent screening episodes. Consenting women aged 46 to 68 attending the regional Breast Screening Service were randomly assigned to conventional digital mammography (DM, control arm) or DBT in addition to DM (DBT, study arm). At the subsequent round all participants underwent DM. Thirty‐six months follow‐up allowed for the identification of cancers detected in the subsequent screening and interscreening interval. Relative risk (RR) and 95% confidence interval (95% CI) were computed. Cumulative CD and Nelson‐Aalen incidence were analysed over the follow‐up period. Between 31 December 2014 and 31 December 2017, 43 022 women were randomised to DM and 30 844 to DBT. At baseline, CD was significantly higher (RR: 1.44, 95% CI: 1.21‐1.71) in the study arm. ICD did not differ significantly between the two arms (RR: 0.92, 95% CI: 0.62‐1.35). At subsequent screening with DM, the CD was lower (nearly significant) in the study arm (RR: 0.83, 95% CI: 0.65‐1.06). Over the follow‐up period, the cumulative CD (comprehensive of ICD) was slightly higher in the study arm (RR: 1.15, 95% CI: 1.01‐1.31). The Nelson‐Aalen cumulative incidence over time remained significantly higher in the study arm for approximately 24 months. Benign lesions detection was higher in the study arm at baseline and lower at subsequent tests. Outcomes are consistent with a lead time gain of DBT compared to DM, with an increase in false positives and moderate overdiagnosis.

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BackgroundIt has been documented that variations exist in breast cancer treatment despite wide dissemination of clinical practice guidelines. The aim of this population-based study was to evaluate the impact of regional guidelines (Piedmont guidelines, PGL) for breast cancer diagnosis and treatment on quality-of-care indicators in the Northwestern Italian region of Piedmont.MethodsWe included two samples of women aged 50–69 years with incident breast cancer treated in Piedmont before and after the introduction of PGL: 600 in 2002 (pre-PGL) and 621 in 2004 (post-PGL). Patients were randomly selected among all incident breast cancer cases identified through the hospital discharge records database. We extracted clinical data on breast cancer cases from medical charts and ascertained vital status through linkage with town offices. We assessed compliance with 14 quality-of-care indicators from PGL recommendations, before and after their introduction in clinical practice.ResultsAmong patients with invasive lesions, 77.1% (N = 368) and 77.5% (N = 383) in the pre-PGL and post-PGL groups, respectively, received breast conservative surgery (BCS) as a first-line treatment. Following BCS, 87.7% received radiotherapy in 2002, compared to 87.9% in 2004. Of all patients at medium-to-high risk of distant metastasis, 65.5% (N = 268) and 63.6% (N = 252) received chemotherapy in 2002 and in 2004, respectively. Among the 117 patients with invasive lesions and negative estrogen receptor status in 2002, hormonal therapy was prescribed in 23 of them (19.6%). The incorrect prescription of hormonal therapy decreased to 10.8% (N = 10) among the 92 estrogen receptor-negative patients in 2004 (p < 0.01).Compliance with PGL recommendations was already high in the pre-PGL group, although some quality-of-care indicators did not reach the standard. In the pre/post analysis, 8 out of 14 quality-of-care indicators showed an improvement from 2002 to 2004, but only 4 out of 14 reached statistical significance. We did not find any change in the risk of mortality in the post-PGL versus the pre-PGL group (adjusted hazard ratio 0.94, 95%CI 0.56–1.56).ConclusionsThese results highlight the need to continue to improve breast cancer care and to measure adherence to PGL.

The clinical significance of micropapillary growth pattern in ductal carcinoma in situ is controversial and the impact of nuclear grading in terms of recurrence of this lesion is yet to be clarified. Our aim was to evaluate, on a series of micropapillary in situ carcinomas, the histological features correlated with recurrence and whether the micropapillary subtype had a different behavior from other non-micropapillary ductal carcinoma in situ. We collected 55 cases of micropapillary in situ carcinomas from four institutions. All cases were reviewed for nuclear grade, extent, necrosis, microinvasion and tested for estrogen and progesterone receptors, Ki67, HER2, EGFR and p53 expression. Clinical data, type of surgery and follow up were obtained for all patients. Our results showed that the nuclear grade is crucial in determining the biology of micropapillary carcinoma in situ, so that the high nuclear grade micropapillary ductal carcinoma in situ more frequently overexpressed HER2, showed higher proliferation index, displayed necrosis and microinvasion and was more extensive than low/intermediate nuclear grade. Logistic regression analysis confirmed the high nuclear grade (Odds ratio: 6.86; CI: 1.40-33.57) as the only parameter associated with elevated risk of local recurrence after breast-conserving surgery. However, the recurrence rate of 19 micropapillary carcinoma in situ, which were part of a cohort of 338 consecutive ductal carcinoma in situ, was significantly higher (log-rank test, P-value ¼ 0.019) than that of non-micropapillary, independently of the nuclear grade. In conclusion, although nuclear grade may significantly influence the biological behavior of micropapillary ductal carcinoma in situ, micropapillary growth pattern per se represents a risk factor for local recurrence after breast-conserving surgery.

Several studies suggest that population-based breast cancer screening programmes might help reduce social inequalities in breast cancer survival both by increasing early diagnosis and by improving access to effective treatments. To start disentangling the two effects, we evaluated social inequalities in quality of treatment of screen-detected breast cancer in the city of Turin (Italy). Combining data from the Audit System on Quality of Breast Cancer Treatment and the Turin Longitudinal Study, we analysed 2700 cases in the screening target age class 50-69 diagnosed in the period 1995-2008. We selected 10 indicators of the pathway of care, relative to timeliness and appropriateness of diagnosis and treatment, and three indicators of socioeconomic position: education, occupational status and housing characteristics. For each indicator of care, relative risks of failure were estimated by robust Poisson regression models, controlling for calendar period of diagnosis, size of tumour and activity volume of the surgery units. The principal predictor of failure of the good care indicators was the calendar period of diagnosis, with a general improvement with time in the quality of diagnosis and treatment, followed by size of the tumour and volume of activity. Socioeconomic indicators show only a marginal independent effect on timeliness indicators. The observed associations of quality indicators with socioeconomic characteristics are lower than expected, suggesting a possible role of the screening programme in reducing disparities in the access to good-quality treatments thanks to its capability to enter screen-detected women into a protected pathway of care.