Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Wong, Natalie Z.; Abelson, Jonathan S.; Milsom, Jeffrey W.; Yeo, Heather

doi:10.1016/j.clcc.2018.01.003

Cited by 42 publications

(35 citation statements)

References 23 publications

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“…A study by Simin et al published in 2017 assessed that HRT ever-use is associated with a 10% decreased risk of all gastrointestinal cancers; in particular in liver and colon cancers, the reduction of risk is statistically significant (0.81, CI 0.65–0.99, for liver and 0.90, CI 0.84–0.95, for colon) [6]. A recent study in 2018 showed a reduction of risk of colorectal cancer (0.81, p = 0.005) and also a reduction in death from colorectal cancer (HR 0.63, p = 0.002) and all-cause mortality (0.76, p = 0.001) in HRT users [31]. A possible explanation of the influence of HRT on colon cancer is the predominance of receptors of estrogens in the colon, which seems to lose expression during carcinogenesis.…”

Section: Hrt and Colon-rectal Cancer (Crc)mentioning

confidence: 99%

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy

et al. 2019

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Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptoms and has been shown to prevent bone loss and fracture. The progestogen is added to provide endometrial protection in women with an intact uterus. After the publication of the initial WHI (Women’s Health Initiative) results in 2002 reporting an overall increased risk of breast cancer, many women discontinued HRT. Despite the re-analysis of the results by subgroups of patients and updates with extended follow-up, much controversy remains, which we will analyze later in the text. Different types of estrogen or progestogen, as well as different formulations, doses, and durations, may play a role in HRT’s effects on breast tissue. Evidence states that conjugated equine estrogen (CEE), compared to estro-progestin therapy, shows a better profile risk (HR 0.79, CI 0.65–0.97) and that, among different type of progestins, those structurally related to testosterone show a higher risk (RR 3.35, CI 1.07–10.4). Chronic unopposed endometrial exposure to estrogen increases the risk of endometrial hyperplasia and cancer, whereas the association with progestins, especially in continuous combined regimen, seems to reduce the risk (RR 0.71, CI 0.56–0.90). HRT was also associated with a protective effect on colon cancer risk (HR 0.61, CI 0.42–0.87). Data about ovarian and cervical cancer are still controversial.

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Section: Hrt and Colon-rectal Cancer (Crc)mentioning

confidence: 99%

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy

et al. 2019

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“…The blood levels of these hormones are known to be reduced by metformin. Recent clinical data showed that hormone replacement therapy (HRT) in women might reduce CRC risk, suggesting possible opportunities for translational research [50]. Growth hormone (GH) therapy and autonomous hyperproduction of GH together with increased level of IGF-1 are associated with a higher risk for CRC, and close follow-up for these patients is highly advised [51].…”

Section: Discussionmentioning

confidence: 99%

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma

Powell

Cempirkova

Dundr

et al. 2020

Translational Oncology

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BACKGROUND: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a possible association of diabetes mellitus and other comorbidities and their treatment with progression of colorectal cancer. PATIENTS AND METHODS: We investigated the correlation between pathological characteristics and clinical course, including comorbidities in 1004 Czech patients diagnosed and surgically treated for colorectal adenocarcinoma (CRC) between 1999 and 2016. RESULTS: In our data set, CRC patients treated with metformin due to coexisting diabetes mellitus type 2 (T2DM) developed fewer distant metastases which clinically correlates with slower CRC progression. Survival in metformin subgroup was longer, particularly in men with CRC. Osteoporosis may be a negative factor of survival in CRC patients. CONCLUSIONS: Our findings also indicate that aging, higher tumor grade and TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecular responses and with various epigenetic characteristics. More awareness and increased understanding of the mechanisms underlying the positive effect of metformin on patients' survival could offer insight into new treatment methods and permit more individualized treatment plans.

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“…Moreover, it is not surprising to notice that the prediction of bevacizumab-induced hypertension for survival outcomes was age- and gender-dependent. As evidenced, aging-related methylation can influence the gene expression of key control genes in colorectal cancer and adenoma [ 35 ], and hormone replacement therapy was significantly associated with reduced risk of colorectal cancer incidence and improved colorectal cancer-specific survival in female patients [ 36 ]. We agree that further studies are needed to obtain the biological proof and confirm the current findings.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of bevacizumab-induced hypertension in patients with metastatic colorectal cancer: an updated meta-analysis

Zhang

et al. 2018

Aging

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We tested the hypothesis that bevacizumab-induced hypertension may be a useful predictor for objective response rate, progression-free and overall survival in patients with metastatic colorectal cancer via a comprehensive meta-analysis. Search process, article selection and data extraction were independently performed by two investigators. Statistical analyses were conducted using the STATA/SE software. Fourteen independent studies and 2292 study subjects were synthesized. Overall relative risk of objective response rate for bevacizumab-induced hypertension was 2.03 (95% confidence interval [CI]: 1.18-3.48, p=0.01), with significant heterogeneity and publication bias, whereas unbiased estimate was nonsignificant after considering potentially missing studies. Overall hazard ratio for progression-free survival was 0.58 (95% CI: 0.43-0.77, p<0.001), with significant heterogeneity and publication bias, and unbiased estimate was significant (hazard ratio: 0.52, 95% CI: 0.41-0.66, p<0.001). Overall hazard ratio for overall survival was 0.51 (95% CI: 0.39-0.65, p<0.001), and this estimate was not likely confounded by heterogeneity or publication bias. Subgroup and meta-regression analyses suggested that hypertension grade of controls, sample size, age and gender were possible causes of heterogeneity. Taken together, our findings indicate that bevacizumab-induced hypertension can predict progress-free survival and overall survival in patients with metastatic colorectal cancer, whereas its prediction for objective response rate was nonsignificant.

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Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Cited by 42 publications

References 23 publications

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy

Current Evidence of the Oncological Benefit-Risk Profile of Hormone Replacement Therapy

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma

Usefulness of bevacizumab-induced hypertension in patients with metastatic colorectal cancer: an updated meta-analysis

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