Reproductive risk factors and oestrogen/progesterone receptor-negative breast cancer in the Breast Cancer Family Registry.

BACKGROUND: Oestrogen receptor (ER)- and progesterone receptor (PR)-negative (ER-PR-) breast cancer is associated with poorer prognosis compared with other breast cancer subtypes. High parity has been associated with an increased risk of ER-PR- cancer, but emerging evidence suggests that breastfeeding may reduce this risk. Whether this potential breastfeeding benefit extends to women at high risk of breast cancer remains critical to understand for prevention. METHODS: Using population-based ascertained cases (n=4011) and controls (2997) from the Breast Cancer Family Registry, we examined reproductive risk factors in relation to ER and PR status. RESULTS: High parity (≥3 live births) without breastfeeding was positively associated only with ER-PR- tumours (odds ratio (OR)=1.57, 95% confidence interval (CI), 1.10-2.24); there was no association with parity in women who breastfed (OR=0.93, 95% CI 0.71-1.22). Across all race/ethnicities, associations for ER-PR- cancer were higher among women who did not breastfeed than among women who did. Oral contraceptive (OC) use before 1975 was associated with an increased risk of ER-PR- cancer only (OR=1.32, 95% CI 1.04-1.67). For women who began OC use in 1975 or later there was no increased risk. CONCLUSIONS: Our findings support that there are modifiable factors for ER-PR- breast cancer and that breastfeeding in particular may mitigate the increased risk of ER-PR- cancers seen from multiparity.

Tumour morphology predicts PALB2 germline mutation status.

BACKGROUND: Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status. METHODS: Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations. RESULTS: Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0-64.6; P=5 × 10(-7)). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers. CONCLUSION: This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2.

Testing for her2 in breast cancer: current pathology challenges faced in Canada.

This review is designed to highlight several key challenges in the diagnosis of human epidermal growth factor receptor 2 (her2)-positive breast cancer currently faced by pathologists in Canada: Pre-analysis issues affecting the accuracy of her2 testing in non-excision sample types: core-needle biopsies, effusion samples, fine-needle aspirates, and bone metastasesher2 testing of core-needle biopsies compared with surgical specimensCriteria for retesting her2 status upon disease recurrenceLiterature searches for each topic were carried out using the medline, Embase, International Pharmaceutical Abstracts, and biosis databases. In addition, the congress databases of the American Society of Clinical Oncology (2005-2011) and the San Antonio Breast Cancer Symposium (2007-2011) were searched for relevant abstracts.All authors are expert breast pathologists with extensive experience of her2 testing, and several participated in the development of Canadian her2 testing guidelines. For each topic, the authors present an evaluation of the current data available for the guidance of pathology practice, with recommendations for the optimization or improvement of her2 testing practice.

Treatment patterns of elderly breast cancer patients at two Canadian cancer centres.

BACKGROUND: Treatment of breast cancer in elderly women is limited by declining functional status and life expectancy. The impact of providing less aggressive treatment remains controversial. This study assessed the treatment patterns of elderly breast cancer patients. METHODS: Retrospective chart review of women ≥70 y with breast cancer treated between 2004 and 2011 at two large Canadian cancer centres. Tumour and treatment characteristics were collected across three subgroups: 70-74 y (n = 314), 75-79 y (n = 233), and ≥80 y (n = 219). Comparisons were made using Chi-squared test, Fisher-Freeman-Halton exact test, or ANOVA. Disease free (DFS) and overall (OS) survival were estimated by Kaplan-Meier analysis and compared by log-rank test. RESULTS: Women ≥80 y had larger tumours that were better differentiated, hormone receptor-positive, HER2-negative, and lymph node (LN)-positive relative to younger women (p < 0.05). Women ≥80 y more frequently underwent mastectomy than breast conserving surgery and lacked LN staging (p < 0.05). Chemotherapy was provided in few patients, especially ≥80 y. Radiation therapy was provided less often in women ≥80 y despite indications. Hormone therapy was more frequently provided in women ≥80 y. Women ≥80 y had a significantly lower DFS (17.5 m) relative to women 70-74 y (31 m, p = 0.02) and 75-79 y (35 m, p = 0.006). Women ≥80 y had the lowest median OS (53 m) relative to 70-74 y (79 m, p = 0.001) and 75-79 y (75 m, p = 0.003) women. CONCLUSIONS: Women ≥80 y received less aggressive treatment than younger women and had less favourable DFS and OS. Until age-specific recommendations are available physicians must use clinical judgement and assess the tumour biology with the patient's comorbidties to make the best choice.

The effect of increasing copper content in phosphate-based glasses on biofilms of Streptococcus sanguis.

This paper reports the effect of a series of phosphate-based glasses based on the Na(2)O-CaO-P(2)O(5) system doped with increasing amounts of copper and the effect of this increasing copper content on the viability of an in vitro biofilm of Streptococcus sanguis over an 8 day period in a constant depth film fermenter. The addition of copper to the glass caused the solubility to change, so the glasses were adjusted in order that their solubility in artificial saliva was nominally the same (0.3062 +/- 0.07 mg cm(-2) h(-1)). Initial experiments on glasses with 1.5% and 10% copper showed that after 6 h there was no statistical difference between the copper containing glasses and the non-copper containing glass and HA in terms of the viability of the biofilms. However, at 24 h there was an approximately 0.8-0.9 log reduction in viability of the biofilms grown on the 5% copper glass and an approximately 1.0-1.3 log reduction for the 10% copper containing glass. Further experiments on the glass with 10% copper and another glass with 15% copper were carried out in a time dependent study. For both glasses a clear decrease in viable counts at 24 h was found but for both glasses these returned to levels similar to those of controls. The initial decrease in viability during the first 24 h is likely to be due to the antibacterial effect of the copper and this could be correlated with copper content. The recovery after 24 h is probably due to the dead cells forming a barrier, making diffusion of the antibacterial ions, increasingly difficult. This study has shown that phosphate-based glasses could potentially be used to deliver antibacterial ions to help combat oral infections. Copper, which has been shown to have antibacterial properties, could be incorporated but some development of the glasses used in this investigation may be required. Further work is needed to determine the effectiveness of copper containing glasses on oral bacterial communities.

Effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis.

Silver is a powerful antibacterial ion that may be useful for dealing with localized infections, such as periodontitis. However, the use of silver in this role could be significantly improved by the development of an effective means of delivery. Phosphate-based glasses may provide a means of delivering the ions in a controlled manner. In our study, we have examined the effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis. Glasses of nominally the same dissolution rate were doped with silver at 1, 5,10, and 15 mol % and the number of colony-forming units (CFUs) determined after 6 and 24 h in a constant depth film fermenter (CDFF). The 1 mol % silver showed little change between 6 and 24 h. However, only 0.5 log CFUs were present on the glass containing 5 mol % at 6 h, and this reduced to virtually zero at 24 h. Few viable bacteria were found on the 10 mol % glass at both 6 and 24 h. The 15 mol % glass was investigated in this experiment, but no viable counts were detected. In a second set of experiments, glasses with 10 and 15 mol % silver were tested in the CDFF for up to 192 h. For the 10 mol % silver glass, there was approximately 0.8 log CFUs on this glass, which dropped to almost zero at 50 h. This was approximately 1.5-2.0 log reduction in CFUs compared to controls, and this difference was maintained for the first 50 h. After 50 h, there was a slow increase in the CFUs on all samples. However, CFUs on the 10 mol % silver glass were still suppressed up to 192 h compared to the controls. However, both controls also exhibited a decrease in viable counts at 50 h; this may have been due to carryover of silver into the control sample holders. However, this was minimized by the specimen layout in the CDFF and by having gaps between specimen sets. For the 15 mol % silver glass, counts for both this glass and the controls decreased to virtually zero between 24 and 48 h, but the numbers slowly increased up to 170 h, but the number of CFUs was suppressed compared to the 10 mol % glass at the same time point. The decrease seen is clearly the effect of the silver ions; however, the slow increase in CFUs may be accounted for by the biofilms forming thick layers on top of the glass discs inhibiting the release of ions from the glass by forming a "sacrificial layer" through which further ions have to diffuse.

Granular cell tumour of the breast: MRI findings and review of the literature.

Granular cell tumours (GCTs) are uncommon, usually benign neoplasms that can mimic malignancy on breast imaging. GCTs can originate anywhere in the body but are most frequently found in the head and neck area, particularly in the oral cavity. When occurring in the breast, as occurs in 5-8% of all cases of GCT, the clinical presentation is similar to that of a primary breast carcinoma. We report a case of granular cell tumour of the breast presenting as a suspicious lesion on breast imaging, and review the MRI features of GCTs.