Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

The shifting trajectory of growth in femur length during gestation

Bone size is a determinant of bone strength and tracks in its percentile of origin during childhood and adolescence. We hypothesized that the ranking of an individual's femur length (FL) is established in early gestation and tracks thereafter. Fetal FL was measured serially using 2D ultrasound in 625 Norwegian fetuses. Tracking was assessed using Pearson correlation, a generalized estimating equation model, and by calculating the proportion of fetuses whose FL remained within the same quartile. Baseline FL Z-score (weeks 10 to 19) and later measurements correlated, but more weakly as gestation advanced: r = 0.59 (weeks 20 to 26); r = 0.45 (weeks 27 to 33); and r = 0.32 (weeks 34 to 39) (p<0.001). Tracking within the same quartile throughout gestation occurred in 13% of fetuses. Of the 87% deviating, 21% returned to the quartile of origin, so 34% began and ended in the same quartile, 38% deviated by one quartile, and 28% deviated by two or more quartiles by the end of gestation. A standard deviation higher baseline FL Z-score, placental weight (150 g), maternal height (5 cm), and weight (10 kg), was associated with a 0.25, 0.15, 0.10, and 0.05 SD higher FL Z-score at the end of gestation, respectively (p ranging from <0.001 to 0.02). Tracking within the same percentile throughout the whole of gestation, as suggest by growth charts, is uncommon. Deviation from tracking is more common and is the result of changes in growth velocity within and between fetuses and is partly influenced by maternal, fetal, and placental factors. © 2010 American Society for Bone and Mineral Research

Remodeling markers are associated with larger intracortical surface area but smaller trabecular surface area: A twin study

All postmenopausal women become estrogen deficient but not all remodel their skeleton rapidly or lose bone rapidly. As remodeling requires a surface to be initiated upon, we hypothesized that a volume of mineralized bone assembled with a larger internal surface area is more accessible to being remodeled, and so decayed, after menopause.We measured intracortical, endocortical and trabecular bone surface area and microarchitecture of the distal tibia and distal radius in 185 healthy female twin pairs aged 40 to 61. years using high-resolution peripheral quantitative computed tomography (HR-pQCT). We used generalized estimation equations to analyze (i) the trait differences across menopause, (ii) the relationship between remodeling markers and bone surface areas, and (iii) robust regression to estimate associations between within-pair differences.Relative to premenopausal women, postmenopausal women had higher remodeling markers, larger intracortical and endocortical bone surface area, higher intracortical porosity, smaller trabecular bone surface area and fewer trabeculae at both sites (all p < 0.01). Postmenopausal women had greater deficits in cortical than trabecular bone mass at the distal tibia (-0.98 vs. -0.12 SD, p < 0.001), but similar deficits at the distal radius (-0.45 vs. -0.39 SD, p = 0.79). A 1 SD higher tibia intracortical bone surface area was associated with 0.22-0.29 SD higher remodeling markers, about half the 0.53-0.67 SD increment in remodeling markers across menopause (all p < 0.001). A 1 SD higher porosity was associated with 0.20-0.30 SD higher remodeling markers. A 1 SD lower trabecular bone surface area was associated with 0.15-0.18 SD higher remodeling markers (all p < 0.01). Within-pair differences in intracortical and endocortical bone surface areas at both sites and porosity at the distal tibia were associated with within-pair differences in some remodeling markers (p = 0.05 to 0.09).We infer intracortical remodeling may be self perpetuating by creating intracortical porosity and so more bone surface for remodeling to occur upon, while remodeling upon the trabecular bone surface is self limiting because it removes trabeculae with their surface. © 2011 Elsevier Inc

Leisure time physical activity and risk of non-vertebral fracture in men and women aged 55 years and older : the Tromso Study

Our aim was to examine associations between leisure time physical activity and risk of non-vertebral fractures in men and women aged ≥55 years, with focus on the anatomical fracture location. Self-reported physical activity was registered in 3,450 men and 4,072 women aged 55–97 years at baseline in the Tromsø Study, Norway, in 1994–1995. Non-vertebral fractures were registered through December 31, 2009. During 75,546 person-years at risk, 1,693 non-vertebral fractures were identified. Risk of any non-vertebral fracture decreased with increasing physical activity level in men (P trend = 0.006) and non-significantly in women (P trend = 0.15), after adjustment for age, body mass index, height, smoking, and previous fracture. The reduced fracture risk was due to a reduced risk in the weight-bearing skeleton, particular at the hip, whereas risk of fracture in the non-weight-bearing skeleton was not related to physical activity. At weight-bearing sites, an inverse relationship between physical activity and fracture risk was present in both sexes (P trend ≤ 0.013). Compared with sedentary subjects, the most active men and women had respectively 37% (HR = 0.63, 95% CI: 0.45, 0.88) and 23% (HR = 0.77, 95% CI: 0.62, 0.95) reduced fracture risk in the weight-bearing skeleton. Physical activity is associated with reduced fracture risk at weight-bearing sites, with no associations at non-weight-bearing sites, in both sexes. Habitual physical activity is an important amendable approach to prevent hip fracture

Impact of Osteoporotic Fracture Type and Subsequent Fracture on Mortality: The Tromsø Study

Summary - Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival. Introduction - Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures. Methods - The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables. Results - Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73–2.42 in women and 2.49, 95% CI 2.00–3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21–1.84 and 1.81, 95% CI 1.37–2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52–2.35 and 1.77, 95% CI 1.16–2.71), respectively. Conclusion - Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention

Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population-based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age-adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2-1.5) in women, and 2.0 (95% CI, 1.6-2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50-59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk. © 2013 American Society for Bone and Mineral Research. © 2013 American Society for Bone and Mineral Research

Concordance between the predicted and observed risk of non-vertebral osteoporotic fracture (upper panel) and hip fracture (lower panel) in the Tromsø Study cohort, according to the Garvan nomograms.

<p>(A): Quintile cut-offs for the predicted 10-year risk (%) of non-vertebral osteoporotic fracture in women were: 10.8, 15.3, 21.2 and 31.9 for model with BMD (M1); and 12.5, 16.3, 21.3 and 31.5 for model with weight (M2). Corresponding cut-offs in men were 5.3, 8.0, 11.7 and 18.3 for M1; and 5.9, 8.3, 12.1, 17.9 for M2. Quartile cut-offs for the predicted 10-year risk (%) of hip fracture in women were: 1.3, 2.6, 4.9 and 11.2 for M1 and 1.7, 2.9, 5.0 and 11.1 for M2; In men, 0.3, 0.8, 1.6 and 3.9 for M1; and 0.9, 1.5, 2.6 and 4.8 for M2. (B): Quintile cut-offs for the predicted 5-year risk (%) of non-vertebral osteoporotic fracture in women were: 5.2, 7.4, 10.5 and 16.4 for model with BMD (M1); and 6.2, 8.1, 10.8 and 16.5 for model with weight (M2). Corresponding cut-offs in men were 2.8, 4.2, 6.3 and 10.0 for M1; and 3.2, 4.5, 6.6, 10.1 for M2. Quartile cut-offs for the predicted 5-year risk (%) of hip fracture in women were: 0.7, 1.4, 2.7 and 5.8 for M1 and 0.9, 1.6, 2.8 and 6.3 for M2; In men, 0.2, 0.4, 0.8 and 2.1 for M1; and 0.5, 0.8, 1.4 and 2.7 for M2.</p