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Prior studies have observed a link between night shift work and increased risk of breast cancer. Melatonin, a hormone related to circadian rhythm, has been proposed to lower breast cancer risk by inhibiting cell proliferation. The disruption of peak melatonin that occurs during night shift work could explain the increase in risk observed. Several studies have assessed whether higher melatonin levels are associated with decreased breast cancer risk, but results have been conflicting. We examined the relationship between urinary melatonin levels and breast cancer risk in a nested case-control study conducted within the Women’s Health Initiative Observational Study. First morning urine samples collected at baseline were assayed for melatonin levels in 258 women diagnosed with invasive breast cancer and 515 matched controls from three enrollment sites. Using conditional logistic regression to adjust for matching factors and established risk factors, results indicate no association between urinary melatonin levels and breast cancer risk. The mean creatinine adjusted melatonin levels for cases and controls were 16.30 ng/mg and 16.05 ng/mg, respectively. Compared to the lowest quartile of creatinine adjusted melatonin, the odds of breast cancer did not vary by quartile of creatinine adjusted melatonin, adjusted for known breast cancer risk factors: second quartile 0.84 (95% CI 0.52-1.38), third quartile 1.05 (95% CI 0.65-1.72) and fourth quartile 1.09 (95% CI 0.66-1.81). This study does not suggest that melatonin is protective against breast cancer and suggests that reasons other than melatonin suppression may explain the increased risk of breast cancer seen in night shift workers.

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Indiana University-Purdue University Indianapolis (IUPUI)

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Excerpt: Manganiello et al., (2010) aimed to evaluate the sexual functioning of mastectomy patients and its association with their quality of life. There are two shortcomings with this study that render its conclusions invalid, or at least, weakly supported.

Breast cancer is the second most common cancer in women in the United States, accounting for approximately 30% of newly diagnosed female cancers every year. In 2023, it is estimated that around 297,790 invasive breast cancers will be diagnosed as new cases with nearly 43,700 women deaths. The average lifetime risk of a woman in the United States accruing a breast cancer diagnosis is approximately 13%, meaning that there is a 1 in 8 chance of developing breast cancer. Classification of breast cancers is distinguished based on the presence of three receptors: HER2, estrogen, and progesterone. Absence of these receptors is categorized as triple negative breast cancer and accounts for about 15% of all breast cancers, thus is the most aggressive and difficult to treat. In this study, research involving two flavonoids, CT1 and CT3 show cytotoxic effects against cell lines MCF7 (ER+, PR+, HER2-) and SKBr3 (ER-, PR-, HER2+), that represent the most common breast cancers. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor, followed by isolation and purification by chromatography. The cells were seeded and then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 mM for cytotoxicity assays, and 40mM for analysis of mechanism of action via immunoblotting and TUNEL. These two flavonoids differ on the presence of a double bond between positions 2 and 3. At the concentrations tested, CT1 has cytotoxic activity against MCF7 but no significant effect on SKBr3, while CT3 has cytotoxic activity against SKBr3 but not on MCF7. CT1 and CT3 target the activated forms of ERK, c-JUN and SP6; however, the effect of CT1 appears to be significantly stronger than CT3 and does not involve the survival pathway. CT1 and CT3 inhibit cell viability in MCF7 and SKBr3 breast cancer cells by activating an extrinsic apoptotic pathway. Additional studies using a triple negative breast cancer cell line has shown that this activation is independent of the presence of estrogen and progesterone receptors or the upregulation of HER2.

After a mastectomy due to breast cancer, a woman faces a choice about whether to undergo cosmetic reconstruction of her breast(s). In choosing reconstruction, women restore not only their bodies but their socially acceptable selves. In spite of this, most choose not to have reconstructive surgery. Though they are in the majority, not much is known about these women, and about what they do to navigate through life with a body that does not meet expectations of femininity. In this project, I use the case of women who choose not to have reconstruction and not to simulate their missing breast(s) to explore the boundaries of the socially acceptable body. Drawing on interviews with women who did not have reconstruction, examination of depictions of bodies on breast cancer organization web sites, and content analysis of their discussion board postings, I analyze women’s choices not to reconstruct their breasts and place those choices in the context of modern breast cancer culture, which promotes an ideal ‘survivor’ body. I find that these women emphasize concerns about stigma and authenticity and that these concerns are expressed through appearance changes that vary across public and private settings. This research extends our understanding of deviant bodies to understanding the stigma of socially incomprehensible bodies. Further, it makes explicit the assumptions about selfhood that are implied by both current popular perception and sociological work on stigmatization.

Indiana University-Purdue University Indianapolis (IUPUI) / The aldehyde dehydrogenase (ALDH) superfamily comprises a group of NAD(P)+-dependent enzymes that catalyze the conversion of aldehydes to their corresponding carboxylic acids. Of the nineteen human ALDH enzymes, members of the ALDH1A subfamily consisting of ALDH1A1, ALDH1A2, and ALDH1A3 have attracted interest as markers of cancer stem cells (CSCs) in several cancer types including lung, breast, and ovarian. CSCs represent a distinct subpopulation of highly tumorigenic cells that promote metastasis, recurrence, and resistance to conventional cancer therapies. The increased expression and activity of ALDH1A in CSCs is well-documented, as is the correlation between ALDH1A and a more aggressive cancer phenotype with poorer treatment outcomes. However, the actual functional role of ALDH1A in the context of CSCs has yet to be clearly defined. Elucidating this role will lead to a greater understanding of CSC biology and evaluate ALDH1A as a potential anti-CSC therapeutic target. In this study, previously developed and characterized selective small-molecule inhibitors of ALDH1A were used in conjunction with global transcriptomic, proteomic, and metabolomic analyses to identify pathways that could potentially establish a link between ALDH1A activity and early events in CSC formation in a triple-negative breast cancer (TNBC) model. These approaches revealed that ALDH1A inhibition is associated with mitochondrial and metabolic dysfunction and perturbation of the electron transport chain. ALDH1A inhibition also resulted in an increase in markers of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), specifically mediated through the Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway. These effects appear to occur independently of both the canonical function of ALDH1A in detoxifying reactive aldehydes as well as its potential metabolic contribution through the generation of NADH. Together, these results suggest a separate role for ALDH1A in TNBC CSCs in protecting against ER stress that warrants further study. / 2024-10-03