The P.I.N.K. Study Approach for Supporting Personalized Risk Assessment and Early Diagnosis of Breast Cancer.

Breast cancer is a clear example of excellent survival when it is detected and properly treated in the early stage. Currently, screening of this cancer relies on mammography, which may be integrated by new imaging techniques for more exhaustive evaluation. The Personalized, Integrated, Network, Knowledge (P.I.N.K.) study is a longitudinal multicentric study involving several diagnostic centres across Italy, co-ordinated by the Italian National Research Council and co-funded by the Umberto Veronesi Foundation. Aim of the study is to evaluate the increased diagnostic accuracy in detecting cancers obtained with different combinations of imaging technologies, and find the most effective diagnostic pathway matching the characteristics of an individual patient. The study foresees the enrolment of 50,000 women over the age of 40 years presenting for breast examination and providing informed consent to data handling. So far, the 15 participating centres across Italy have recruited a total of 22,848 patients. Based on the analyses of the first 175 histopathological-proven breast cancers, mammographic sensitivity was estimated to be 61.7% (n = 108 cancers), whereas diagnostic accuracy increased by 35.5% (n = 44 cancers) when mammography was integrated with other imaging modalities (ultrasound and/or digital breast tomosynthesis). Increase was mainly determined by ultrasound alone. Given the ongoing data collection and recruitment, the number of cancers detected is too low to allow any further in-depth analysis to explore links to patient characteristics. Past studies show that the uniform approach of population screening guidelines should be revised in favour of more personalised regimens, where known standards are integrated by imaging techniques most suitable for the individual's characteristics. With the ultimate goal of identifying early breast cancer detection strategies, our preliminary results suggest that integrated diagnostic approach could lead to a paradigm shift from an age-based regimen toward more specific and effective risk-based personalised screening regimens, in order to reduce mortality from breast cancer.

Granular cell tumor of the breast: Molecular pathology and clinical management.

Granular cell tumor is a rare condition that occasionally affects breast parenchyma: approximately, 5%-15% of all granular cell tumors represent 1:1000 of breast tumors. In this study, we reported a consecutive series of 12 patients with primary granular cell tumor of the breast observed at our institute, focusing attention on preoperative management, surgical approach, and long-term follow-up. Eight cases (8/12; 66.78%) presented with left-breast tumors; in the majority of patients (11/12; 91.7%), the lesion was identified in one of the upper quadrants. Specifically, upper intern quadrants (10 cases) were more affected. Surgical excision was performed in all patients. Mean diameter at pathologic section was 11.4 mm (range: 5-22). Tumor relapse was reported only in one case (8.3%). Mean follow-up was 98.1 months (range: 1-192). We proposed a model to explain the molecular mechanism of granular cell tumorigenesis associating to the high level of S100 protein. Management of primary granular cell tumor of the breast requires a correct initial diagnosis using breast imaging associated with core biopsy. Surgical procedure with wide resection or quadrantectomy requires a careful evaluation of breast margins.

The biological features and prognosis of breast cancer diagnosed during pregnancy: a case-control study.

BACKGROUND: Breast cancer during pregnancy (BCP) is relatively rare and is associated with controversies about its biology and prognosis. Hence, we designed a case-control study to examine tumor features and outcome in a series of BCP patients diagnosed and treated in a single institution. MATERIAL AND METHODS: We identified 65 patients diagnosed with BCP and for each; we selected two non-pregnant breast cancer patients, who were matched for age, year of surgery, stage, and neoadjuvant chemotherapy. We then compared the differences in pathology, immunohistochemical features (ER, PR, HER2 and ki-67), disease-free (DFS) and overall survival (OS). RESULTS: We did not find any significant differences in tumor characteristics between the two groups. However, at a median follow-up of four years, BCP patients had an inferior DFS (HR 2.3; 95% CI 1.3-4.2), after adjustment for possible confounding covariates. No difference in OS was observed. However, upon restricting the analysis to patients who did not receive neoadjuvant chemotherapy, patients with BCP had inferior OS as well (HR 2.6; 95% CI 1.0-6.5). No association between induction of abortion and prognosis was observed. CONCLUSIONS: While we did not observe any differences in tumor features, BCP patients have poorer prognosis compared to age and stage-matched control. Further studies should try to elucidate reasons for such poor outcome.

Breastfeeding in breast cancer survivors: pattern, behaviour and effect on breast cancer outcome.

Little is known regarding the safety and feasibility of breastfeeding in women with a history of breast cancer. We have performed a survey among breast cancer patients who completed their pregnancy following breast cancer management to examine their lactation behaviours and its effect on breast cancer outcome. Out of 32 women identified, 20 were reachable and accepted to take the questionnaire. Ten women initiated breastfeeding, 4 stopped within one month and 6 had long-term success with a median period of 11 months (7-17 months). The latter were all previously subjected to breast conserving surgery and received qualified lactation counselling at delivery. The main reasons for not initiating breastfeeding were "uncertainty regarding maternal safety" and "a priori unfeasibility" expressed either by the obstetrician or by the oncologist. At a median follow-up of 48 months following delivery, all 20 women were alive with two relapses; one in each group (i.e., lactating and non-lactating). This analysis adds to the limited available evidence on the feasibility and safety of breastfeeding in breast cancer survivors. Proper fertility and survivorship counselling is crucial and requires more attention in breast cancer clinics.

A rare cause of mastalgia: Dercum's disease (adiposis dolorosa).

Among the symptoms reported by patients undergoing breast imaging, pain is one of the most common. Mastalgia is generally classified as cyclic, noncyclic, or extramammary. A rare cause of breast pain is Dercum's disease, or adiposis dolorosa, a condition characterized by multiple, often painful subcutaneous lipomas. Painful breast lipomas have not been described in the literature so far. The diagnosis is made by clinical means supported by diagnostic imaging. We report the case of a 58-year-old postmenopausal woman affected by Dercum's disease in the breast. Ultrasound examination showed multiple oval, well-defined, hyperechoic lesions suggestive of breast lipomas. No significant features were detected by mammography.

Radiological features and pathological-biological correlations in 348 women with breast cancer under 35 years old.

The aim of this study was to present mammography and ultrasound features, and accuracy, in 348 young women (under 35 years old) with breast cancer, and to determine whether such features could be correlated with pathological and biological factors. We performed a retrospective review of the radiological, pathological and biological features of women under 35 years old with breast cancer who were seen in our institute between January 2000 and December 2002. A total of 348 women were analysed. The sensitivity of mammography was 84.9% and that of ultrasound was 88%. There is a statistically significant positive correlation between the high sensitivity of ultrasound and the histology type (P=0.004) as well as the expression of PgR (P=0.01). Also, there is a correlation between the sensitivity of mammography and the histology type (P=0.004). Microcalcifications are associated with age (P=0.05) and overexpression of HER2/neu (P=0.007). Ultrasound may be the appropriate initial imaging test for symptomatic young women, and mammography may be useful in confirming the features, although there was no significant difference in the accuracy of the two tests. Histological and biological profiles may be correlated with imaging sensitivity.

Analogic versus digital mammographic examination a radiological study of mammary microcalcifications on 52 surgical samples.

PURPOSE: Digital mammography is known to have lower spatial resolution compared to conventional analogic mammography. The aim of this study was to evaluate whether this physical feature could compromise the perception of microcalcifications in radiological findings. MATERIALS AND METHODS: Fifty-two surgical samples of non-palpable breast lesions with microcalcifications were imaged using both techniques. The images were examined by four different radiologists. Data processing was limited to comparing the number of microcalcifications found on the conventional and digital images, in both standard and magnified modality. The cases were classified into 3 groups according to the number of calcifications demonstrated in the surgical sample: less than 10, 10 to 30, and more than 30. The differences in the count of microcalcifications with the two acquisition modalities were evaluated with the Kappa test. In order to compare the differences we synthesised by percentage those cases exhibiting a larger or lesser number of calcifications. RESULTS: The Kappa test was 0.546 in standard analogic vs standard digital, 0.582 in magnified analogic vs magnified digital, 0.828 in standard analogic vs magnified analogic and 0.492 in standard digital vs magnified digital. The most significant results were observed on comparing the magnifications produced with the two modalities: in 25% of cases, digital magnification detected more calcifications than did traditional magnification. The number of cases where standard digital images allowed the detection of more calcifications than standard analogic images was significant, although less important (17.8%). CONCLUSIONS: The study was able to provide data that confirm the overall equivalence of the two techniques, as far as subtle mammographic findings (such as microcalcifications) are concerned. In particular, as applied to the series we examined, there is a cautious advantage in favour of the digital technique. More clinical studies, on larger series, will be necessary for a further and more thorough comparison of the two techniques, so that the results might be consistently useful in clinical practice.