Reproductive risk factors associated with breast cancer in young women by molecular subtype

BackgroundFew studies have examined detailed features of pregnancy and the postpartum period as potential risk factors for early onset breast cancer (BC) by molecular subtype. These data may have value for improving risk assessment and prevention.MethodsWe surveyed parous enrollees in the prospective Mayo Clinic Breast Disease Registry (MCBDR) who had been diagnosed with BC at age <55 years between 2015 and 2020. Summary statistics were used to describe survey responses and reproductive risk factors by BC subtype (defined by estrogen/progesterone receptors and human epidermal growth factor receptor expression, nurse-abstracted from the medical record). Associations were assessed with Kruskal-Wallis and Chi-Square tests, followed by age-adjusted linear and logistic regression models. We compared results from this parous cohort to those from a separate cohort of nulliparous MCBDR participants with BC diagnosed at age <55 years.ResultsIn 436 parous respondents with subtype data abstracted, we identified a higher frequency of BRCA1 mutation, earlier age at diagnosis, and lower BI in patients with triple negative BC. Comparing parous to nulliparous young women with breast cancer, the proportion with TNBC was larger in the latter (12.2% vs. 15.1%, p = 0.03).ConclusionsEarly age at diagnosis and deleterious BRCA1 mutation were more frequent among TNBC patients. In addition, parous young women with TNBC had a lower BI than those with other BC subtypes, a hypothesis-generating finding that supports the need for additional research on the cycle of pregnancy-lactation-postpartum involution and BC etiology.     

Immunization with BLS-Stx2B chimera totally protects dams from early pregnancy loss induced by Shiga toxin type 2 (Stx2) and confers anti-Stx2 immunity to the offspring

Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved in food-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC and is responsible for systemic complications including Hemolytic Uremic Syndrome (HUS). It has been previously demonstrated that Shiga toxin type 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. The main purpose of this study was to determine if an active immunization prevents Stx2 mediated pregnancy loss and confers passive protective immunity to the offspring. For that purpose Sprague Dawley female rats were immunized with the chimera based on the enzyme lumazine synthase from Brucella spp. (BLS) and the B subunit of Shiga toxin 2 (Stx2B) named BLS-Stx2B. After immunization females were mated with males. At day 8 of gestation, dams were challenged intraperitoneally with a sublethal and abortifacient dose of Stx2. The immunization induced high anti-Stx2B-specific antibody titers in sera and most important, prevented pregnancy loss. Pups born and breastfeed by immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fostering experiments indicated that passive protective immunity against Stx2 was transmitted through lactation. These results indicate that immunization of adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss and confers anti Stx2 protective immunity to the offspring.     

TIDAL WAVES: Network mechanisms in the neuroendocrine control of prolactin release

Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons tonically inhibit pituitary release of the hormone, prolactin. Through the powerful actions of prolactin in promoting lactation and maternal behaviour while suppressing sexual drive and fertility, TIDA neurons play a key role in reproduction. We summarize insights from recent in vitro studies into the membrane properties and network behaviour of TIDA neurons including the observations that TIDA neurons exhibit a robust oscillation that is synchronized between cells and depends on intact gap junction communication. Comparisons are made with phasic firing patterns in other neuronal populations. Modulators involved in the control of lactation – including serotonin, thyrotropin-releasing hormone and prolactin itself – have been shown to change the electrical behaviour of TIDA cells. We propose that TIDA discharge mode may play a central role in tuning the amount of dopamine delivered to the pituitary and hence circulating prolactin concentrations in different reproductive states and pathological conditions.     

穿刺冲洗术治疗哺乳期乳腺脓肿182例疗效观察及治疗后哺乳结局分析

目的 探讨哺乳期乳腺脓肿经超声引导下穿刺冲洗术治疗效果,并分析影响治疗后病人哺乳结局的相关因素。方法收集2017年1月至2020年12月郑州大学第三附属医院收治经超声引导下穿刺冲洗术治疗的182例哺乳期乳腺脓肿病人的临床资料,哺乳结局根据治疗后是否回奶,分为回奶组27例和继续母乳喂养组155例。从产次、产后时间（产后初次发病时间）、脓肿位置、脓肿长径、致病菌、穿刺次数等方面,采用χ2检验进行单因素分析,采用logistic回归模型进行哺乳结局的多因素分析。结果 本研究纳入182例病人,其中165例经过超声引导下穿刺冲洗术联合抗生素治疗后达到治愈标准,治愈率90.7%,治疗后回奶病人27例,回奶率14.8%(27/182)。单因素分析结果显示,哺乳结局与时间、脓肿位置、穿刺次数有相关性（均P<0.05）;多因素分析结果显示,中央区脓肿[OR=11.61,95%CI:(2.70,49.85),P=0.001]、脓腔≥5 cm[OR=3.60,95%CI:(1.12,11.51),P=0.031]和穿刺次数[OR=10.08,95%CI:(2.04,49.60),P=0.004]是影响...     

Impact of bariatric surgery on breastfeeding: a systematic review

Metabolic and bariatric surgery helps women achieve a healthier weight, reduce co-morbid conditions, increase fertility rates, and improve pregnancy outcomes compared with counterparts who are obese. Breastfeeding is known to provide both infant and maternal health benefits as well. Less is known about the impact of bariatric surgery on breastfeeding. The objective of this study was to review the impact of bariatric surgery on breastfeeding following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed and Medline databases were searched using terms such as “bariatric surgery,” “postnatal care,” “lactation,” and “breastfeeding.” Reference lists were also used to find relevant articles. A total of 49 records were identified. Abstracts were screened, and 11 observational studies were identified after meeting inclusion criteria, which included the use of original research on breastfeeding and women who have had bariatric surgery. The available research shows that breast milk after bariatric surgery is adequate in nutrients and that no long-term effects were reported in cases studies when nutrient deficiencies were corrected. Limitations include observational study design and small sample sizes. This systematic review suggests that breastfeeding after bariatric surgery should be recommended along with monitoring and micronutrient supplementation. However, additional research and increased sample sizes are needed to further examine the relationship, and such studies should be conducted to strengthen the evidence and explore ways to improve breastfeeding rates in this population.     

Lactation and Maternal Risk of Type 2 Diabetes: A Population-based Study

Background

Lactation has been associated with improvements in maternal glucose metabolism.

Methods

We explored the relationships between lactation and risk of type 2 diabetes in a well-characterized, population-representative cohort of women, aged 40-78 years, who were members of a large integrated health care delivery organization in California and enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008. Multivariable logistic regression was used to control for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index while examining the impact of duration, exclusivity, and consistency of lactation on risk of having developed type 2 diabetes.

Results

Of 2233 women studied, 1828 were mothers; 56% had breastfed an infant for ≥1 month. In fully adjusted models, the risk of type 2 diabetes among women who consistently breastfed all of their children for ≥1 month remained similar to that of women who had never given birth (odds ratio [OR] 1.01; 95% confidence interval [CI], 0.56-1.81). In contrast, mothers who had never breastfed an infant were more likely to have developed type 2 diabetes than nulliparous women (OR 1.92; 95% CI, 1.14-3.27). Mothers who never exclusively breastfed were more likely to have developed type 2 diabetes than mothers who exclusively breastfed for 1-3 months (OR 1.52; 95% CI, 1.11-2.10).

Conclusions

Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life. Mothers should be encouraged to exclusively breastfeed all of their infants for at least 1 month.     

Delayed physical and neurobehavioral development and increased aggressive and depression-like behaviors in the rat offspring of dams fed a high-fat diet

Early maternal exposure to a high-fat diet (HFD) may influence the brain development of rat offspring and consequently affect physiology and behavior. Thus, in the present study, we investigated the somatic, physical, sensory-motor and neurobehavioral development of the offspring of dams fed an HFD (52% calories from fat, mainly saturated) and the offspring of dams fed a control diet (CD – 14.7% fat) during lactation from the 1st to the 21st postnatal day (P). Maternal body weights were evaluated during lactation. In the progeny, somatic (body weight, head and lengths axes) and physical (ear unfolding, auditory conduit opening, eruption of the incisors and eye opening) development and the consolidation of reflex responses (palm grasp, righting, vibrissa placing, cliff avoidance, negative geotaxis, auditory startle response and free-fall righting) were determined during suckling. Depressive and aggressive behaviors were tested with the forced swimming test (FST) and the “foot-shock” test on days 60 and 110, respectively. The open field test was used to assess motor function. Compared to controls, the HFD-pups exhibited decreases in body weight (P7–P21) and body length (P4–P18), but by days P71 and P95, these pups were overweight. All indicators of physical maturation and the consolidation of the following reflexes, vibrissa placing, auditory startle responses, free-fall righting and negative geotaxis, were delayed in HFD-progeny. In addition, the pups from HFD dam rats also exhibited reduced swimming and climbing times in the FST and increased aggressive behavior. No changes in locomotion were observed. These findings show developmental and neurobehavioral changes in the rat offspring of dams fed the HFD during lactation and suggest possible disruption of physical and sensory-motor maturation and increased susceptibility to depressive and aggressive-like behavior.