Trends of breast cancer incidence and risk factor prevalence over 25 years

SummaryIntroduction To examine the trends in the prevalence of breast cancer risk factors in relation to breast cancer incidence trends and to explore whether the changes in risk factors differed by ethnicity in Hawaii over a 25-year period.Methods We pooled 17 population-based epidemiological studies conducted in Hawaii between 1975 and 2001. The study population of 82,295 women included subjects of Caucasian, Japanese, Native Hawaiian, Chinese, and Filipino ancestry. We computed age-adjusted prevalence estimates by ethnic group for 5-year time periods. Logistic regression was used to evaluate trends over time.Results The prevalence of an early age at menarche, nulliparity, and parity of fewer than three children, but not that of a late age at first live birth, increased during the study period. Whereas current smoking decreased for all ethnicities over time, the age-adjusted prevalence of overweight, obesity, college education, and alcohol use increased. Trends differed by ethnicity. For Native Hawaiians, the prevalence of overweight, obesity, alcohol use and nulliparity rose over time. For Japanese, the prevalence of overweight, early age at menarche, and having fewer than three children increased. Caucasians showed an increasing prevalence of overweight, obesity, college education, and nulliparity. In Filipina women, we observed changes in reproductive behavior and increasing obesity.Conclusions Despite a slowing trend for some breast cancer risk factors, the overall risk profile in this population may lead to further increases in breast cancer incidence. Different ethnic groups may benefit from specific prevention strategies.     

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer

Background:

It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.

Methods:

We conducted a case–control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.

Results:

Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P_trend=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P_trend=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.

Conclusion:

Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.     

Depression and cancer risk: 24 years of follow-up of the Baltimore Epidemiologic Catchment Area sample

Objective  

The objective was to characterize the relationship between depression and incident cancer. Few studies have employed population-based prospective data on subtypes of cancer to address the question.     

Evolution of sites of recurrence after early breast cancer over the last 20 years: implications for patient care and future research

Improvements in adjuvant therapy have led to a sustained fall in recurrences after early breast cancer. The differential reduction in local and systemic recurrences is poorly understood. This study aimed to explore changes in the distribution of loco-regional and distant recurrences in clinical trials reported over the last 20 years. We also aimed to determine the relative impact of adjuvant chemotherapy and endocrine therapy. MEDLINE search for adjuvant, phase III randomized breast cancer clinical studies between January 1990 and March 2011 was performed. Neoadjuvant, single agent biologics and studies that did not report the proportion of loco-regional and distant recurrences were excluded. The change in the frequency of recurrences was assessed as the nonparametric correlation between the number of loco-regional recurrences as a proportion of all recurrences and time. Studies were weighted by sample size. The differential effect of chemotherapy and endocrine therapy was also assessed. Fifty-three randomized clinical trials with a total of 86,598 patients were included in the analysis. Between 1990 and 2011, the proportion of loco-regional recurrences has decreased from approximately 30 to 15 % (Spearman’s ρ = ?0.40, p < 0.001). There was no interaction between type of surgery (mastectomy vs. lumpectomy), administration of adjuvant radiation therapy and menopausal status and the correlation of loco-regional recurrences and time. Chemotherapy regimen showed a larger negative correlation compared with endocrine therapy ( ρ = 0.49 vs. ρ = 0.24). Advances in treatment of early breast cancer have differentially reduced the proportion of loco-regional recurrences compared with distant recurrences. In recent trials, loco-regional recurrences account for less than 10–15 % of all recurrences. These falling event rates may affect patient care, especially when deciding on treatments influencing loco-regional control. This change may also impact on the design of clinical trials assessing loco-regional therapy such as surgery and/or local radiation therapy.     

Boiled coffee consumption and the risk of prostate cancer: follow-up of 224,234 Norwegian men 20–69 years

Background:

There is insufficient epidemiological evidence on the relationship between type of coffee and the risk of prostate cancer.

Methods:

The risk of prostate cancer by use of boiled vs not boiled coffee were assessed in a prospective study of 224,234 men 20–69 years. 5740 incident prostate cancers were identified.

Results:

With no coffee as reference group the hazard ratios of <1–4, 5–8 and 9+ cups per day of boiled coffee only were 0.84 (0.73–0.96), 0.80 (0.70–0.92) and 0.66 (0.55–0.80), P-trend=0.00. The corresponding figures for not boiled coffee were 0.89 (0.80–0.99), 0.91 (0.81–1.02) and 0.86 (0.74–1.00), P-trend=0.22.

Conclusion:

An inverse relationship between number of cups per day and the risk of prostate cancer was present only for the boiled coffee type.     

Serum levels of sex hormones and breast cancer risk in premenopausal women: a case–control study (USA)

High levels of serum estrogens and androgens have been convincingly linked with an increased risk of breast cancer among postmenopausal women. By contrast, the role of blood levels of these hormones in the etiology of premenopausal breast cancer is not well understood. In a case-control study, we sought to examine associations between levels of serum estradiol, sex-hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and progesterone and risk of premenopausal breast cancer. Cases of breast cancer under age 45 were identified using rapid ascertainment systems in Seattle/Puget Sound, Washington and control subjects were identified from the same area through random digit dialing methods. A total of 169 eligible breast cancer cases and 195 control subjects donated blood (either before or six or more weeks after surgery) and were interviewed using a standardized questionnaire. The fully adjusted risk ratios and 95% confidence intervals for the highest versus lowest tertiles of estradiol, according to menstrual cycle phase, were 3.10 (0.8-12.7) for early follicular, 0.54 (0.2-1.7) for late follicular and 0.60 (0.3-1.4) for luteal. Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4-1.6) for SHBG, 2.42 (1.1-5.2) for DHEA, 1.12 (0.6-2.5) for testosterone, and 1.33 (0.6-2.8) for androstenedione. For luteal progesterone, the RR for the highest versus lowest tertile was 0.55 (0.2-1.4). In summary, we did not find a convincing association between serum SHBG, estradiol, testosterone or androstenedione and premenopausal breast cancer risk. Observed differences between cases and controls subjects in serum levels of DHEA and luteal phase progesterone should be investigated further in large prospective studies.     

Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20–44 years of age

Aspects of reproductive history are among the most well-established breast cancer risk factors. However, relatively little is known about how they influence risk of different molecular subtypes of breast cancer, particularly among younger women. Using data from a population-based case–control study of women 20–44 years of age, we assessed the relationships between various reproductive factors and risk of estrogen receptor positive (ER+), triple-negative, and HER2-overexpressing breast cancers. Detailed reproductive histories were obtained through structured interviewer administered in-person questionnaires. Reproductive histories among control women (n = 941) were compared to those of ER+ cases (n = 781), triple-negative cases (n = 180), and HER2-overexpressing cases (n = 60) using polytomous logistic regression. Age at menarche, parity, and number of full-term pregnancies were similarly associated with risk of all three breast cancer subtypes. In contrast, age at first live birth, the interval between age at menarche and age at first birth, and breastfeeding were inversely associated with risk of triple-negative breast cancer (P values for trend 0.002, 0.006 and 0.018, respectively), but were not associated with risk of ER+ or HER2-overexpressing cancers. A strong inverse association between breastfeeding and risk of triple-negative breast cancer has now been consistently observed across numerous studies, and at present it is the most well-established protective factor for this aggressive and lethal form of breast cancer. Further studies clarifying the biological mechanisms underlying this relationship and confirming our results with respect to age at first birth and the interval between age at menarche and age at first birth are needed.     

Doubling of testicular cancer incidence rate over the last 20 years in southern France

In recent decades, testicular cancer incidence has considerably increased in a majority of industrialized countries. In France, short reports suggested that the testicular cancer incidence rate has also risen, especially in north-eastern regions. In Europe, geographical variation of incidence rates has been observed in Baltic countries and a clear birth cohort effect has been revealed. This study aimed to assess temporal trends in testicular cancer incidence in southern France. We examined incidence rates over a 20-year time period in a series of 506 consecutive cases of testicular cancer recorded from 1980 to 1999 in the Midi-Pyrenees region of France. Age, calendar period, and birth cohort effects were examined simultaneously using Poisson regression models. Our analysis found a significant rise in the overall incidence rate of testicular germ cell tumors from 1.27 to 3.04 per 100,000 between 1980–1984 and 1995–1999, an annual increase of 5.70%. These results, the first obtained in a large series in southern Europe, show a twofold increase in incidence rate of testicular cancer in the Midi-Pyrenees region, which is very similar to that observed in all European countries, more or less doubling in the last 20 years. Interestingly, this major jump and the apparent testicular cancer gradient between northern and southern Europe suggest considerable geographical heterogeneity in incidence, but low geographical variation in temporal trends.     

Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case–control study

Previous epidemiological studies evaluated endogenous sex hormone levels and colorectal cancer (CRC) risk have yielded inconsistent results. Also, it is unknown if consumption of dietary isoflavones may influence the endogenous sex hormones and CRC relationships. We conducted a nested case–control study within the JPHC Study Cohort II wherein 11,644 women provided blood samples at the 5-year follow-up survey. We selected two matched controls for each case from the cohort (185 CRC cases and 361 controls). Multivariable conditional logistic regression was used to estimate odds ratios (ORs), 95% confidence intervals (CIs) for the association between circulating sex hormone levels and CRC risk. Comparing extreme tertiles, circulating testosterone levels were positively associated with CRC risk (OR = 2.10, 95% CI = 1.11–3.99, p for trend = 0.03). Levels of estradiol, SHBG, and progesterone were not associated with CRC risk. In a subgroup analysis by dietary isoflavone intake, SHBG levels were positively associated with CRC risk among those with low total isoflavone intake (p for trend = 0.03), with a statistically nonsignificant inverse association among those with high total isoflavone intake (p for trend = 0.22; p for interaction = 0.002). Endogenous levels of testosterone were positively associated with CRC among postmenopausal women. The association of endogenous SHBG with CRC development may be altered by the level of dietary isoflavone intake.     

Unemployment risk 2 years and 4 years following gastric cancer diagnosis: a population-based study

Purpose

The needs of gastric cancer survivors have received limited attention. Returning to work after gastric cancer has not yet been described in a population-based study. We aimed to examine the unemployment risk at 2 and 4 years after gastric cancer.

Methods

The present historical prospective cohort study included baseline measurements from the Israeli Central Bureau of Statistics 1995 National Census, with follow-up until 2011. A group with gastric cancer and an age-, sex-, and ethnicity-matched control group were sampled from the census population. Binary logistic regression analyses were used to assess odds ratios (ORs) for the study outcomes, controlling for socioeconomic factors, and employment status at 2 years before diagnosis.

Results

Data for 152 gastric cancer cases and 464 matched controls were analyzed. Those who died during the study period were excluded. Two years after diagnosis, 53.3 % of gastric cancer survivors and 43.8 % of controls were unemployed (p = 0.04); 4 years after diagnosis, 53.9 % of survivors, and 47.2 % of controls were unemployed (p = 0.15). In the adjusted models, gastric cancer was only associated with unemployment 2 years after diagnosis (OR = 1.47, 95 % confidence interval [CI] = 1.02–2.12). This association weakened and lost significance 4 years after diagnosis (OR = 1.42, 95 % CI = 0.89–2.28). Gastric cancer was not associated with decreased income at 2 (OR = 1.48, 95 % CI = 0.91–1.48) or 4 years (OR = 1.65, 95 % CI = 0.99–2.74) after diagnosis.

Conclusions

Gastric cancer survivorship was associated with unemployment 2 years after diagnosis. Longer-term survivors may have the prospect of returning to work.

Implications for cancer survivors

For patients with cancer, returning to work may be an indicator for returning to a normal lifestyle after serious illness. This study highlights the need for early social support in gastric cancer survivors to promote faster recovery.

     

γ-Glutamyl transferase and breast cancer risk

Background:

It has been reported that there is an increased risk of cancer in individuals with elevated levels of serum γ-glutamyl transferase (GGT).

Methods:

In the Guernsey Breast Cancer Cohort Study, GGT was measured in sera from 1803 normal women. Among these women, 251 subsequently developed cancer, of whom 96 developed breast cancer.

Results:

After adjustment for age at entry, height, weight, age at menarche and first birth with nulliparity, there was a highly significant relationship between elevated GGT and breast cancer risk. In the highest quartile, the hazard ratio (HR) was 2.17 (95% confidence interval (CI): 1.19, 3.93). When subdivided by menopausal status, there was a reduced non-significant effect in postmenopausal women, whereas for premenopausal women in the highest quartile, HR was 3.81 (95% CI: 1.37, 10.59). Premenopausal women with serum GGT levels above the normal range had a significantly elevated HR of 4.90 (95% CI: 1.86, 12.94).

Conclusions:

These results suggest that premenopausal women with high normal (above median) serum GGT or elevated levels (⩽40 IU l⁻¹) are at increased risk of breast cancer and might benefit from close surveillance, possibly with breast magnetic resonance imaging scans. Serum GGT may mark previous exposure to carcinogens and lead to the identification of DNA adducts involved in mammary carcinogenesis.     

Occupation and breast cancer in women 20–44 years of age (United States)

Objective: To examine the relation between breast cancer risk and job history among women 20–44 years of age who participated in a multi-center, population-based, case–control study. Methods: Participants consisted of women newly diagnosed with breast cancer (1642) and controls identified by random-digit dialing (1494). Details about the three longest jobs were collected and coded by an industrial hygienist. Odds ratios and 95% confidence intervals were calculated and adjusted for age, study site, and other breast cancer risk factors. Results: Several occupational and industrial categories were found to influence breast cancer risk. Stratification of the study population by parity revealed differences in breast cancer risk between the two groups for several occupational categories, including teachers, librarians or counselors (increased risk only among parous women) and natural scientists and mathematicians (decreased risk only among nulliparous women). Conclusions: This is among the first population-based case–control studies to examine occupational history and breast cancer risk in young women, with the ability to consider a wide array of potential confounders, including reproductive characteristics. This study provides further evidence of an increased breast cancer risk for several occupations and industries. Other findings were not as strongly supported by previous investigations.     

Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast cancer: Results of a prospective study

Purpose

To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy.

The changing patterns of bladder cancer in Egypt over the past 26 years

Objective To evaluate temporal changes in histopathological types of bladder cancer and to assess associated changes in demographic, epidemiologic, and lifestyle risk factors. Methods We abstracted data from all available medical records from the National Cancer Institute of Cairo University (NCI-Cairo). Six calendar years representing 5-year periods between 1980 and 2005 were evaluated. Information on demographics, schistosomal infection, clinical symptoms of bladder cancer, and tumor pathology was abstracted. Results During this 26-year period, important changes in the frequency of histopathological types of bladder cancer occurred. We found a statistically significant association between time period of diagnosis and histopathological type. Patients diagnosed in 2005 had a sixfold higher odds associated with transitional cell carcinoma compared to those patients diagnosed in 1980 (odds ratio (OR) 6.00 (95% CI 4.00–8.97)). Conclusions These data strongly suggest that the histopathological profile of bladder cancer in Egypt has changed significantly over the past 26 years. Historically, squamous cell carcinoma was the predominant form of bladder cancer in Egypt; however transitional cell carcinoma has become the most frequent type. These results corroborate findings from a few small-scale hospital-based studies which conclude that the etiology of bladder cancer in Egypt has changed significantly over the past 26 years.     

Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know

Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.