Collaborative Reanalysis Of Individual Data Research Articles

The first national public breast cancer screening program in Saudi Arabia

BACKGROUND AND OBJECTIVES:Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia.METHODS:Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed.RESULTS:Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis.CONCLUSIONS:Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.

Cervical Carcinoma and Sexual Behavior: Collaborative Reanalysis of Individual Data on 15,461 Women with Cervical Carcinoma and 29,164 Women without Cervical Carcinoma from 21 Epidemiological Studies

Abstract High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend <0.001). The relative risk for ≥6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2.27 [95% confidence interval (95% CI), 1.98-2.61] and increased to 2.78 (95% CI, 2.22-3.47) after additional conditioning on reproductive factors. The risk of invasive cervical carcinoma increased with earlier age at first intercourse (P for linear trend <0.001). The relative risk for age at first intercourse ≤14 versus ≥25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors. CIN3/carcinoma in situ showed a similar association with lifetime number of sexual partners; however, the association with age at first intercourse was weaker than for invasive carcinoma. Results should be interpreted with caution given the strong correlation between sexual and reproductive factors and the limited information on HPV status. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1060–9)

Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16 573 women with cervical cancer and 35 509 women without cervical cancer from 24 epidemiological studies

Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16 573 women with cervical cancer and 35 509 women without cervical cancer from 24 epidemiological studies

Letters/Editorial

Letters/Editorial

Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16 573 women with cervical cancer and 35 509 women without cervical cancer from 24 epidemiological studies

Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use. Individual data for 16,573 women with cervical cancer and 35,509 without cervical cancer were reanalysed centrally. Relative risks of cervical cancer were estimated by conditional logistic regression, stratifying by study, age, number of sexual partners, age at first intercourse, parity, smoking, and screening. Among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]). The risk declined after use ceased, and by 10 or more years had returned to that of never users. A similar pattern of risk was seen both for invasive and in-situ cancer, and in women who tested positive for high-risk human papillomavirus. Relative risk did not vary substantially between women with different characteristics. The relative risk of cervical cancer is increased in current users of oral contraceptives and declines after use ceases. 10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.

Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies

Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies

Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: Collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies

Squamous cell carcinomas account for about 80% of cancers of the uterine cervix, and the majority of the remainder are adenocarcinomas. There is limited evidence on the extent to which these histological types share a common etiology. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 8,097 women with invasive squamous cell carcinoma, 1,374 women with invasive adenocarcinoma and 26,445 women without cervical cancer (controls) from 12 epidemiological studies. Compared to controls, the relative risk of each histological type of invasive cervical cancer was increased with increasing number of sexual partners, younger age at first intercourse, increasing parity, younger age at first full-term pregnancy and increasing duration of oral contraceptive use. Current smoking was associated with a significantly increased risk of squamous cell carcinoma (RR = 1.50, 95% CI: 1.35-1.66) but not of adenocarcinoma (RR = 0.86 (0.70-1.05)), and the difference between the two histological types was statistically significant (case-case comparison p < 0.001). A history of screening (assessed as having had at least one previous nondiagnostic cervical smear) was associated with a reduced risk of both histological types, but the reduction was significantly greater for squamous cell carcinoma than for adenocarcinoma (RR = 0.46 (0.42-0.50) and 0.68 (0.56-0.82), respectively; case-case comparison, p = 0.002). A positive test for cervical high-risk HPV-DNA was a strong risk factor for each histological type, with 74% of squamous cell carcinomas and 78% of adenocarcinomas testing positive for HPV types 16 or 18. Squamous cell and adenocarcinoma of the cervix share most risk factors, with the exception of smoking.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full-term pregnancies, and age at first full-term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full-term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full-term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53-2.02) for > or => or =7 full-term pregnancies compared with 1-2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full-term pregnancy among parous women. Early age at first full-term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full-term pregnancies, the RR for first full-term pregnancy at age <17 years compared with > or => or =25 years was 1.77 (95% CI: 1.42-2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26-2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high-risk human papilloma virus (HPV)-positive cases and controls. No relationship was found between cervical HPV positivity and number of full-term pregnancies, or age at first full-term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies

Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p<0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p<0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p<0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking.

Review: breastfeeding is associated with reduced risk of breast cancer

(2002) Lancet 20, 187. Collaborative Group on Hormonal Factors in Breast Cancer. . Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including...

Breast Cancer and Breastfeeding: Collaborative Reanalysis of Individual Data from 47 Epidemiological Studies in 30 Countries, Including 50 302 Women With Breast Cancer and 96 973 Women Without the Disease

Breast Cancer and Breastfeeding: Collaborative Reanalysis of Individual Data from 47 Epidemiological Studies in 30 Countries, Including 50 302 Women With Breast Cancer and 96 973 Women Without the Disease

Review: breast cancer is associated with a family history of the disease in first degree relatives

Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986...

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease.

Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50302 women with invasive breast cancer and 96973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and women's ages when their first child was born, as well as by study and menopausal status. Women with breast cancer had, on average, fewer births than did controls (2.2 vs 2.6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9.8 vs 15.6 months). The relative risk of breast cancer decreased by 4.3% (95% CI 2.9-5.8; p<0.0001) for every 12 months of breastfeeding in addition to a decrease of 7.0% (5.0-9.0; p<0.0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries.

Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease

Women with a family history of breast cancer are at increased risk of the disease, but no study has been large enough to characterise reliably how, over women's lives, this risk is influenced by particular familial patterns of breast cancer. This report, on the relevance of breast cancer in first-degree relatives, is based on combined data from 52 epidemiological studies. Individual data on breast cancer in first-degree relatives (mothers, sisters, and daughters) of 58209 women with breast cancer and of 101986 controls were collected, checked, and analysed centrally. Risk ratios for breast cancer were calculated by conditional logistic regression, stratified by study, age, menopausal status, number of sisters, parity, and age when the first child was born. Breast-cancer incidence and mortality rates for particular family histories were calculated by applying age-specific risk ratios to breast-cancer rates typical for more-developed countries. Altogether 7496 (12.9%) women with breast cancer and 7438 (7.3%) controls reported that one or more first-degree relatives had a history of breast cancer: 12% of women with breast cancer had one affected relative and 1% had two or more. Risk ratios for breast cancer increased with increasing numbers of affected first-degree relatives: compared with women who had no affected relative, the ratios were 1.80 (99% CI 1.69-1.91), 2.93 (2.36-3.64), and 3.90 (2.03-7.49), respectively, for one, two, and three or more affected first-degree relatives (p<0.0001 each). The risk ratios were greatest at young ages, and for women of a given age, were greater the younger the relative was when diagnosed. The results did not differ substantially between women reporting an affected mother (9104) or sister (6386). Other factors, such as childbearing history, did not significantly alter the risk ratios associated with a family history of breast cancer. For women in more-developed countries with zero, one, or two affected first-degree relatives, the estimated cumulative incidence of breast cancer up to age 50 was 1.7%, 3.7%, and 8.0%, respectively; corresponding estimates for incidence up to age 80 were 7.8%, 13.3%, and 21.1%. Corresponding estimates for death from breast cancer up to age 80 were 2.3%, 4.2%, and 7.6%. The age when the relative was diagnosed had only a moderate effect on these estimates. Eight out of nine women who develop breast cancer do not have an affected mother, sister, or daughter. Although women who have first-degree relatives with a history of breast cancer are at increased risk of the disease, most will never develop breast cancer, and most who do will be aged over 50 when their cancer is diagnosed. In countries where breast cancer is common, the lifetime excess incidence of breast cancer is 5.5% for women with one affected first-degree relative and 13.3% for women with two.

Oral Contraceptives and Cancer

Most up-to-date information on oral contraceptives (OCs) and breast cancer risk comes from a collaborative re-analysis of individual data on 53297 cases and 100239 controls. It is now established that there is a moderately increased breast cancer risk among current OC users, which tends to level off in the few years after stopping use. With regard to cervical cancer, OC use has been found to be associated with increased risk in human papilloma virus-positive women. With reference to the well known protective effects of OCs against endometrial carcinogenesis, additional information has suggested a consistent protection across types of OCs used. Further data on ovarian cancer confirm that the protection of OCs is long lasting, and may well be observed 15 to 20 years after stopping use. Several studies have suggested an inverse relationship between use of OCs and risk of colorectal cancer, and in a meta-analysis of published data the pooled relative risk of colorectal cancer for DC ever-use was 0.82 (95% confidence interval 0.74 to 0.97). There was no association with duration of use. The increased risk for hepatocellular carcinoma in the absence of hepatitis B viruses is the only established evidence of a direct association between OC use and cancer risk, which led an International Agency for Research on Cancer Working Group to classify OCs as carcinogenic to humans in 1998.

Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies: Calle E.E.; Heath Jr. C.W.; Miracle-McMahill H.L.; Coates R.J.; Liff J.M.; Franceschi S.; Talamini R.; Chantarakul N.; Koetsawang S.; Rachawat D.; Morabia A.; Schuman L.; Stewart W.; Szklo M.; Bain C; Schofield

Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies: Calle E.E.; Heath Jr. C.W.; Miracle-McMahill H.L.; Coates R.J.; Liff J.M.; Franceschi S.; Talamini R.; Chantarakul N.; Koetsawang S.; Rachawat D.; Morabia A.; Schuman L.; Stewart W.; Szklo M.; Bain C; Schofield

Meta-analysis: Use of combined oral contraceptives in the past 10 years is associated with an increased risk for breast cancer

Source Citation Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer a...

"Breast Cancer and Hormonal Contraceptives: Collaborative Reanalysis of Individual Data on 53,297 Women with Breast Cancer and 100,239 Women without Breast Cancer from 54 Epidemiological Studies".

"Breast Cancer and Hormonal Contraceptives: Collaborative Reanalysis of Individual Data on 53,297 Women with Breast Cancer and 100,239 Women without Breast Cancer from 54 Epidemiological Studies".

Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies

Summary Background The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% Cl] in current users 1·24 [1·15-1·33], 2p<0·00001; 1-4 years after stopping 1·16 [1·08-1·23], 2p=0·00001; 5-9 years after stopping 1·07 [1·02-1·13], 2p=0·009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1·01 [0·96-1·05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives: for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0·88 (0·81-0·95; 2p=0·002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90% of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0·5 (95% Cl 0·3-0·7), 1·5 (0·7-2·3), and 4·7 (2·7-6·7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons. Interpretation Women who are currently using combined oral contraceptives or have used them in the past 10 years are at a slightly increased risk of having breast cancer diagnosed, although the additional cancers diagnosed tend to be localised to the breast. There is no evidence of an increase in the risk of having breast cancer diagnosed 10 or more years after cessation of use, and the cancers diagnosed then are less advanced clinically than the cancers diagnosed in never-users.