Consideration of existing data regarding clinical and biochemical risk factors for the development of breast cancer leads to the hypothesis that enhanced insulin-like growth factor I (IGF-I) activity plays a significant role in the development of this disease. Abnormal IGF-I activity may be related to events occurring prenatally, during puberty, or during adult life. Insulin resistance, a common feature in populations characterized by high caloric intake, may result in the amplification of IGF-I action at the tissue level by altering serum concentrations of IGF-I binding proteins. Several approaches toward testing the hypothesis are proposed, and potential opportunities for clinical application are described.
insulin resistance IGF-I breast cancer hypothesis, insulin-like growth factor I breast cancer development, IGF-I binding proteins insulin resistance cancer risk, Kazer insulin resistance breast cancer IGF hypothesis, PCOS insulin resistance breast cancer risk factors, high caloric intake insulin resistance IGF-I amplification, prenatal puberty adult IGF-I activity cancer risk, hyperinsulinemia IGF binding proteins breast cancer etiology, metabolic syndrome breast cancer risk biochemical factors, insulin resistance tissue level IGF-I action cancer
PMID 7543456 7543456 DOI 10.1002/ijc.2910620408 10.1002/ijc.2910620408
Cite this article
Kazer, R. R. (1995). Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis. International journal of cancer, 62(4), 403-406. https://doi.org/10.1002/ijc.2910620408
Kazer RR. Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis. Int J Cancer. 1995;62(4):403-406. doi:10.1002/ijc.2910620408
Kazer, R. R. "Insulin resistance, insulin-like growth factor I and breast cancer: a hypothesis." International journal of cancer, vol. 62, no. 4, 1995, pp. 403-406.
Estrogen receptor (ER) status is an important biomarker in defining subtypes of breast cancer differing in antihormonal therapy response, risk factors and prognosis. However, little is known about association of ER status with various risk factors in the developing world. Our case-control study done in Kerala, India looked at the associations of ER status and risk factors of breast cancer. From 2002 to 2005, 1,208 cases and controls were selected at the Regional Cancer Center (RCC), Trivandrum, Kerala, India. Information was collected using a
InfertilityCancer Risk from Fertility DrugsBreast Cancer Risk FactorsLong-term Follow-up
To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. Long-term, historic-prospective study. Fertility clinic in a university hospital. PATIENT(S): Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. INTERVENTION(S): Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. MAIN OUTCOME MEASURE(S): Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. RESULT(S): Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. CONCLUSION(S): An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.
Jordan SJ et al., 2021·International journal of cancer
A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further \~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
Contraception/ComparisonCervical Cancer RiskCombined vs Progestin-OnlyPopulation-Based Cohort Study
Open Access
To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person-years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval [CI] 1.10-1.29). Increased risks were seen in current or RR 1.30 (95% CI 1.20-1.42) RR 1.40 (95% CI 1.28-1.53), but not RR 0.91 (95% CI 0.78-1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05-1.60) and squamous cancer (RR 1.31, 95% CI 1.19-1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.