Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Abstract Introduction The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. Methods We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. Results After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (P trend = 0.0003) and the ER H-score (P trend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (P trend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both P trend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (P trend = 0.01) and black women (P trend = 0.03) with ER + tumors. Conclusions Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity

Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: a case-control study.

BACKGROUND: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. METHODS: We used multivariable logistic regression analysis to investigate whether age at first birth ( or =25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages > or =55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. RESULTS: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P(heterogeneity) = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity) = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. CONCLUSIONS: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding

Relationship between migraine history and breast cancer risk among premenopausal and postmenopausal women.

Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers

Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort

To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose–response gradient in the risk of cancer of the corpus uteri (P for linear trend=0.03), with women given ⩾2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users

Common ground in collaborative intelligence analysis: an empirical study

This paper reports an empirical exploration of how different configurations of collaboration technology affect peoples’ ability to construct and maintain common ground while conducting collaborative intelligence analysis work. Prior studies of collaboration technology have typically focused on simpler conversational tasks, or ones that involve physical manipulation, rather than the complex sensemaking and inference involved in intelligence work. The study explores the effects of video communication and shared visual workspace (SVW) on the negotiation of common ground by distributed teams collaborating in real time on intelligence analysis tasks. The experimental study uses a 2x2 factorial, between-subjects design involving two independent variables: presence or absence of Video and SVW. Two-member teams were randomly assigned to one of the four experimental media conditions and worked to complete several intelligence analysis tasks involving multiple, complex intelligence artefacts. Teams with access to the shared visual workspace could view their teammates’ eWhiteboards. Our results demonstrate a significant effect for the shared visual workspace: the effort of conversational grounding is reduced in the cases where SVW is available. However, there were no main effects for video and no interaction between the two variables. Also, we found that the “conversational grounding effort” required tended to decrease over the course of the tas

Behavioral Mechanism during Human Sperm Chemotaxis: Involvement of Hyperactivation

When mammalian spermatozoa become capacitated they acquire, among other activities, chemotactic responsiveness and the ability to exhibit occasional events of hyperactivated motility—a vigorous motility type with large amplitudes of head displacement. Although a number of roles have been proposed for this type of motility, its function is still obscure. Here we provide evidence suggesting that hyperactivation is part of the chemotactic response. By analyzing tracks of spermatozoa swimming in a spatial chemoattractant gradient we demonstrate that, in such a gradient, the level of hyperactivation events is significantly lower than in proper controls. This suggests that upon sensing an increase in the chemoattractant concentration capacitated cells repress their hyperactivation events and thus maintain their course of swimming toward the chemoattractant. Furthermore, in response to a temporal concentration jump achieved by photorelease of the chemoattractant progesterone from its caged form, the responsive cells exhibited a delayed turn, often accompanied by hyperactivation events or an even more intense response in the form of flagellar arrest. This study suggests that the function of hyperactivation is to cause a rather sharp turn during the chemotactic response of capacitated cells so as to assist them to reorient according to the chemoattractant gradient. On the basis of these results a model for the behavior of spermatozoa responding to a spatial chemoattractant gradient is proposed

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy