Table 3.
Studies reporting risk of overall cancer and breast cancer among women with SLE
| Study author and years | Study design | Study population and size | Number of breast cancer cases | Results | Study limitations/strength/comments |
|---|---|---|---|---|---|
| Pettersson et al. [16] | Finnish cancer registry—clinical cohort consists of SLE patients from medicine clinics, who were diagnosed with ARA 1971 criteria. These patients were followed over time (total person-years at risk 2340), and breast cancer was ascertained though Finnish Cancer Registry. The comparison group for the study was sex and age-specific cancer incidence rate for overall Finish Cancer Registry | 205 total SLE patients (182 women and 23 men)—age range for the registry not provided | 4 breast cancer cases out of total 13 cancer cases in women (two breast cancers were diagnosed in the same patient). Mean age of women at cancer diagnosis 55 years and overall age range 39–80 years | Overall cancer RR 2.6 (1.5–4.4) Breast cancer RR 2.7 (0.7–6.8) |
Ability to evaluate the influence of cytotatic drugs on cancer limited due to small number of cases. Only relative risk was reported |
| Dupla ML et al. [21] | Clinical Cohort with retrospective analysis of SLE patients at La paz Hospital, Madrid. Using ARA 1982 criteria for SLE diagnosis. Only number of cases reported without risk evaluation | 96 SLE patients (84 were women). Mean age at SLE onset 30 years | One breast cancer diagnosed out of 5 total female cancer cases. Mean age of women 42 years at cancer diagnosis with age range (33–56 years) | Conclusion SLE patients may have the same malignancies as general population after adjustment for age and sex | Information on cytotoxic medicine reported (cyclophosphamide, azathioprine, and vincristine). Small number of cases |
| Sweeney et al. [17] | Clinical cohort assembled from University medical center (Allegheny county Clinical) using revised criteria ARA 1982 for SLE diagnosis. Cancer cases ascertained through postal survey and non-respondent to the survey the cancer ascertainment was done via university medical records. Expected number calculated by regional age-specific incidence from 1985 Allegheny county census data and 1987 Pennsylvania cancer incidence registry data. Person-year risk cohort was multiplied by regional age-specific incidence | 219 SLE patients with age range 29–69 years | 3 out of 6 cases detected with breast cancer, mean age of women with cancer 54 years, age range at dx of cancer (36–65 years) | Overall cancer SIR 1.36 (0.5–2.96) Breast cancer SIR 2.05 (0.42–5.99) |
Small number but evaluated the immunosuppressive agents |
| Abu-Shakra et al. [18] | Clinical cohort assembled from chart review where SLE was diagnosed using ARA 1982 criteria. Patients followed prospectively for 24 years at University of Toronto Lupus Clinic for cancer. Multiple comparison groups used including (i) General population of Ontario, (ii) 1426 patient with RA and (iii) 248 patients with scleroderma | Total SLE patients 724, out of which 627 were females. Mean age at SLE 33.3 years (range 8–83.1 years) with 10 years mean follow-up | 4 out of 21 cancer in women were breast cancer with mean age at cancer diagnosis 57.2 years (range 27–84 years) | Overall cancer SIR 1.08 (0.7–1.62) Breast cancer SIR 0.7 (0.19–1.8) |
Small number of cases not adjusted for potential variables that could influence the disease incidence |
| Mellemkjaer et al. [19] | Clinical cohort of SLE patients from Danish Hospital discharge register linked to cancer registry in Denmark for detection of breast cancer cases. Expected number calculated using national cancer incidence—ICD code used for SLE diagnosis | SLE patients 1585 (83 % women—1315), 71 % women were under age 60 years at entry into cohort | 14 out of 102 total cancer were in the breast. No information provided for mean age of women at diagnosis of cancer | Overall cancer RR 1.3 (1.06–1.58) Breast cancer RR 1 (0.5–1.7) |
Selection bias—hospital discharge patients and limited number |
| Ramsey-Goldman et al. [15] | Chicago Lupus Cohort Clinical using ARA 1982 linked to tumor registry used to ascertain cancer cases. SIR estimated using age, gender, and race stratified cancer incidence from Cook County IL | 616 women with lupus with mean age at SLE 35.3 years (±17.7 SD) | 8 breast cancer cases—mean age of cancer women 51.6 years (±14.5 SD) | Overall cancer SIR 2 (1.4–2.9) Breast cancer SIR 2.9 (1.4–6.4) [among Caucasian women] |
Small no of cases, single-state registry data |
| Sultan et al. [20] | UK Clinical cohort of SLE patients assembled using ARA 1982 that was followed prospectively. Cancer cases were detected using medical notes. SIR calculated using Southeast England population annualized age/gender specific cancer incidence rate | 276 SLE patients (258 were women—93.5 % females)Mean age at SLE 34.7 years and mean time to occurrence of cancer 7.4 years | 3 breast cancer out of total 10 cancer cases. No information provided for age of the patients at cancer diagnosis | Overall cancer SIR 1.16 (0.55–2.13) Breast cancer SIR 1.06 (0.21–5.9) |
Treatment information provided for cyclosporine and cyclophosphamide. Out of ten cases 6 had prednisolone, 4 received azathioprine, 5 were on hydroxychloroquine and 1 had cyclophosphamide. Limited number of cases |
| Nived et al. [24] | Clinical cohort of SLE patients assembled form Swedish National Population registry (1981–1996) and linked to National Cancer registry. Patients were prospectively followed for development of cancer till 1998. SLE diagnosis was based on typical symptoms in at least two organ systems, the presence of typical immunological findings and lack of better diagnosis. SMR calculated based on observed frequencies from age and gender matched general population data from national cancer registry | 116 SLE patients (99 were women), off these only 110 full filled four or more ACR criteria. Median age at diagnosis of SLE was 48 years | No breast cancer detected. Total 11 cancer detected (7 cases were in women).Mean age for women cancer 66 years (range 53–78 years) | Overall cancer SMR for women 1.02 (0.4–2.1) | Treatment information provided. 19 % patients used azathioprine and or cyclophosphamide and 69 % were treated at least once with steroids during the study period. No breast cancer case detected |
| Cibere et al. [7] | Lupus clinical cohort assembled from Saskatchewan (Canada) University-based clinic and hospital data using ARA 1982 criteria. Provincial cancer statistics was used to calculate the expected number. Tumor registry was utilized to ascertain cancers | 297 SLE patients (84 % women). Mean age at SLE 36 years (range 10–80 years) | 4 breast cancer cases. Mean age for all cancer 60 years (range 27–89 years) | Overall cancer SIR 1.59 (1.05–2.32) Breast cancer SIR 1.15 (0.31–2.95) |
Small number of cases |
| Bjornadal et al. [11] | Clinical cohort based on hospitalized SLE patients from Swedish Hospital discharge register data base using ICD codes. Cases ascertained via National Swedish Cancer Register. Expected number obtained by National Swedish Cancer Register rates | 5715 SLE patients (4201 were women). 59 % of women were under age 60 years | 52 breast cancer cases out of total 443 cancer cases. No information provided for age at diagnosis | Overall cancer SIR 1.25 (1.14–1.37) Breast cancer SIR 0.72 (0.54–0.95) |
Small number of cases, selection bias (cohort assembled from hospital discharged registry matched to Swedish Cancer Registry), acute care setting causing detection bias. No validated study for diagnostic code in hospital discharge Register. Low specificity of the SLE would resulted in underestimation of true risk |
| Bernatsky et al. [6] | International clinical cohort of SLE patients from 23 centers where cases were determined through linkage to regional tumor registries. Expected cases determined by multiplying person-years in the cohort by geographically matched age, sex and calendar year-specific cancer rates, and summing over all person-year. Both ARA 1982/1997used for SLE diagnosis | 9547 patients (90 % female 8607) | 73 breast cancer cases detected out of 431 total cancer cases. Out of 431 cases 86 % cancer were diagnosed among women and 52 % of all cancer were diagnosed among women under age 60 years | Overall cancer SIR 1.15 (1.05–1.27) Overall women cancer SIR 1.17 (1.05–1.29) Breast cancer SIR 0.76 (0.60–0.95) |
Largest study cohort for its time. Breast cancer was the most commonly diagnosed cancer |
| Parikh-Patel et al. [5] | Retrospective clinical cohort study assembled from California patient discharge data using ICD codes. Cancer cases detected via California Cancer Registry. Expected number calculated by sex, race, and 5 years age group using rates from general California population | 30,478 patients. 89 % (27,133) were women and 28 % were age 60 years and above | 237 breast cancer cases out of 1053 total cases among women—51 % cases of all cancer and 43 % of breast cancer cases were diagnosed among women age 60 years and above | Overall cancer risk for both genders 1.14 (1.07–1.2) Breast cancer SIR: 0.76 (0.67–0.86) No difference by race Risk was lower for whites Women age less than 30 SIR 5 (1.91–11.3) and 30-44 years SIR 1.18 (0.86–1.58) |
Single-state (CA) Cohort assembled from hospitalized state discharge data—acute care setting causing detection bias Temporality cannot be established in close cohort between the sequence of events No information about treatment or risk factors. A large study enriched with Race/ethnicity. High quality cancer data from state cancer registry |
| Bernatsky et al. [12] | Multicenter international clinical cohort of SLE from 24 centers. Cases determined via regional tumor registries and expected number determined by multiplying person-years in the cohort by geographically matched age, sex, and calendar year-specific cancer rates | 13,492 study population | 112 breast cancer cases out of 632 total cancer. No Information provided for age (only abstract available) | Overall cancer SIR 1.15 (1.06–1.24) Breast cancer SIR 0.70 (0.58–.085) |
Abstract only no additional information available |
| Chen et al. [8] | Taiwan national cohort study a Population-based cohort assembled from National Health Insurance Research Database and represents 99 % of Taiwan’s entire population. Using ARA 1982, cases detected by ICD-710. SLE patients with a history of cancer were excluded from 1996 to 2005. Cancer was detected by Cancer Registry and expected number of cancer cases were calculated using national age, gender, and period specific cancer rate | 11,763 SLE patients (10,394 female—88.4 %).Mean age 34.7 years (SD 15.61), 67 % younger than age 40 years and 88 % female | 45 breast cancer cases out of 228 solid tumors (total cancer 259). Out of total 85 % cases among women, 71 % of cancer diagnosed among patients age 40 years and above | Overall cancer SIR 1.54 (1.52–1.56) Breast cancer SIR 1.55 (1.51–1.60) |
Population-based large cohort that showed enhanced risk of breast cancer among women with SLE. No explanatory variable information provided or adjusted |
| Bernatsky et al. [13] | Five large SLE cohorts—Bernatsky [6], Bjomadal [11], Kang [30], Mellemkjaer [19], Paarikh-Patel [5]—all clinical cohorts | 42,171 female SLE patients | 376 breast cancer, 66 endometrial, 44 ovarian | Overall cancer SIR 0.76 (0.69–0.85) Breast cancer SIR 0.71 (0.55–0.91) |
No information about treatment or risk factors that can influence breast cancer incidence. Lack of subgroup analysis by race or age |
| Dey et al. [14] | Nested Case-cohort design—Lupus clinic cohort London assembled using ARA 1997 criteria. Control SLE patient without cancer age, sex, race, and SLE duration matched. Cases identified through hospital medical records and confirmed histology or autopsy. UK National cancer registry used for cancer detection. Expected number calculated from Thames Cancer Registry 5-year-annualized rated age and gender specific. Control group was assembled to evaluate different marker (serological/clinical) between cases and controls | 595 SLE patients followed up for 32 years | 5 breast cancer cases out of 33 total cancer—91 % cases diagnosed in women and 27 % of cancer diagnosed age 60 years and above. Mean age for these cases at diagnosis of SLE was 33.5 years (SD 12.7) and at diagnosis of cancer was 50.3 years (SD 14.8) | Overall cancer SIR 1.05 (0.52–1.58) female overall cancer SIR 1.03 (0.66–1.40) Breast cancer SIR 0.48 (0.35–0.64)—91 % women were Caucasian |
Overall risk statistically insignificant and limited number of breast cancer cases. Evaluated serologic and immunosuppressive medicine with clinical cases. Reported anti-thyroid antibodies and SLICC damage was associated with cases |
| Bematsky et al. [9] | Multicenter (30) international SLE cohort—linked to regional tumor registries-almost all clinical cohorts no population-based registry | 16,409 SLE patients (90 % females) | 114 breast cancer cases out of 559 female cancers (Overall total cancer cases 644–84 % cancer in women, 41 % cancer among patients age 60 plus) | Overall cancer SIR 3.02 (2.48–3.63) Overall female cancer SIR 1.15 (1.05–1.24) Breast cancer SIR 0.73 (0.61–0.88) |
Large study with the largest lupus patient population. No data on the race or treatment effect evaluated. Breast carcinoma in situ excluded from the cases, no such exclusion reported for control group |