Cancer risk among Danish women with cosmetic breast implants

The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10-15 years after breast implantation. We extended follow-up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow-up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973-95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0-1.4), during a mean follow-up period of 14.4 years (range = 0-30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5-1.0), and an increased risk of non-melanoma skin cancer (SIR = 2.1; 95% CI = 1.5-2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non-melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8-1.2). With respect to other site-specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non-melanoma skin cancer of 1.1 (95% CI = 0.8-1.6), 0.7 (95% CI = 0.4-1.3) and 1.5 (95% CI = 0.8-2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non-melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants.     

Stage of breast cancer at diagnosis among women with cosmetic breast implants

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.     

Cancer surveillance behaviors and psychosocial factors among long‐term survivors of breast cancer

BACKGROUND:

Little is known about cancer surveillance (mammography, clinical breast examination, and pelvic examination) behaviors in long‐term (9‐16 years) breast cancer survivors. This report describes the relation of these behaviors to demographic and clinical characteristics, psychological symptoms, body satisfaction, and social support.

METHODS:

Survivors who had participated in Cancer and Leukemia Group B treatment Trial 8541 completed a survey that included questions on breast cancer surveillance and pelvic examination, psychological well being, body satisfaction, and social support.

RESULTS:

The participation rate was 78% and included 245 breast cancer survivors. Survivors (n = 107; 44%) reported completing breast cancer surveillance (mammography and clinical breast examination) and completing pelvic examination (n = 162; 68%) within recommended guidelines. There were no significant associations between breast cancer surveillance and breast cancer anxiety, depression, stressful life events, body satisfaction, social support, or demographic characteristics. Survivors within recommended guidelines for pelvic examinations were younger (P = .05), married (P = .003), had health insurance (P = .004), and had lower depression scores (P = .005) than survivors who underused or overused pelvic examination. In addition, survivors within recommended pelvic examination guidelines had significantly lower levels of breast cancer anxiety (P = .03) compared with survivors who underused pelvic examination.

CONCLUSIONS:

Many long‐term breast cancer survivors were not within recommended cancer surveillance guidelines. Private health insurance was associated with following recommendations for pelvic examinations, although such a relation did not exist for breast cancer surveillance. The results of this study have implications for the development of educational programs to improve cancer surveillance among the growing population of long‐term breast cancer survivors. Cancer 2009. © 2009 American Cancer Society.     

Cancer incidence in a cohort of Ontario and Quebec women having bilateral breast augmentation

The possibility that women, who receive breast implants for cosmetic purposes, have increased long-term risks of developing cancer continues to be debated. The objective of our study was to prospectively examine cancer incidence among women who received breast implants. A cohort was assembled of 24,558 women, 18 years of age and older, who underwent bilateral cosmetic breast augmentation, and 15,893 women who underwent other cosmetic procedures in Ontario or Quebec between 1974 and 1989. These plastic surgery patients were selected from the same clinics as the implant population. Incident cancers were identified by linking to Canadian registry data up to December 31, 1997. In total, 676 cancers were identified among women who received breast implants compared to 899 expected based on general population rates (standardized incidence ratio (SIR) = 0.75; 95% confidence interval (CI) = 0.70-0.81). Overall cancer incidence rates among women who received breast implants were similar to that of the other plastic surgery patients (relative risk (RR) = 0.91, 95% CI = 0.81-1.02). However, women who received breast implants had lower breast cancer rates than the plastic surgery patients (RR = 0.64, 95% CI = 0.53-0.79). No increased risks were observed among the implant population for any of the other cancer sites examined. Comparisons involving only women who received breast implants found no association between long-term breast cancer incidence and implant site (submuscular vs. subglandular), fill (saline vs. silicone) or envelope (polyurethane-coated or not). In conclusion, women undergoing cosmetic breast augmentation do not appear to be at an increased long-term risk of developing cancer.     

A study of body image in long‐term breast cancer survivors

BACKGROUND:

In this controlled postdiagnosis study, the authors examined various aspects of body image of breast cancer survivors in cross‐sectional and longitudinal designs.

METHODS:

In 2004 and 2007 the Body Image Scale (BIS) was completed by the same 248 disease‐free women who had been treated for stage II and III breast cancer between 1998 and 2002. “Poorer” body image was defined as greater than the 70th percentile (N = 76 women) of the BIS scores in contrast to “better” body image (N = 172 women). Breast cancer survivors were examined clinically in 2004, and their BIS scores were compared with the scores from an age‐matched group of women from the general population.

RESULTS:

In this cross‐sectional study, poorer body image in 2004 was associated significantly with modified radical mastectomy, undergoing or planning to undergo breast‐reconstructive surgery, a change in clothing, poor physical and mental health, chronic fatigue, and reduced quality of life (QoL). In univariate analyses, most of these factors and manually planned radiotherapy were significant predictors of poorer body image in 2007. In multivariate analyses, manually planned radiotherapy, poor physical QoL and high BIS score in 2004 remained independent predictors of a poorer body image in 2007. Body image ratings were relatively stable from 2004 to 2007. Twenty‐one percent of breast cancer survivors reported body image dissatisfaction, similar to the proportion of dissatisfaction in controls.

CONCLUSIONS:

In this cross‐sectional analysis, body image in breast cancer survivors was associated with the types of surgery and radiotherapy and with mental distress, reduced health, and impaired QoL. Body image ratings were relatively stable over time, and the antecedent body image score was a strong predictor of body image at follow‐up. Body image in breast cancer survivors differed very little from that in controls. Cancer 2010. © 2010 American Cancer Society.     

Birth outcome in women with breast cancer

We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0-2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Public health insurance and cancer‐specific mortality risk among patients with breast cancer: A prospective cohort study in China

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer‐specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer‐specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer‐specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow‐up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer‐specific mortality (95% CI 0%‐65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer‐specific mortality (95% CI 11%‐82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%‐12%) reduction in cancer‐specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%‐39%). Our findings suggest that underinsured patients face a higher risk of breast cancer‐specific mortality in developing countries.     

A nationwide epidemiologic study of breast cancer incidence following breast reduction surgery in a large cohort of Swedish women

Summary While it has been demonstrated that prophylactic mastectomy reduces breast cancer incidence among women at high risk, many women often consider this disfiguring surgery unacceptable. One alternative approach may be breast reduction surgery. In order to evaluate the long-term incidence of breast cancer following surgical removal of breast tissue, we have extended by 9 years the follow-up period of our earlier retrospective cohort study of Swedish women electing cosmetic breast reduction surgery (n=30,444) between 1965 and 1993, yielding an average of nearly 16 years of follow-up. Cancer incidence through 2002 was ascertained via the Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated comparing women who underwent breast reduction surgery with women in the general Swedish population. Breast cancer was observed in 443 women versus 624 expected for a statistically significant reduced SIR of 0.71 (95% CI=0.65–0.78). Analyses by age at surgery, time since surgery or calendar year of surgery revealed similar reductions in risk. Our study of over 30,000 women with long-term follow-up offers further evidence that women undergoing breast reduction surgery have reduced breast cancer risk. As the evidence from large-scale cohort studies accumulates, direct testing of this reduction in risk through clinical trials should be considered.     

Predictive factors of the tumor immunological microenvironment for long‐term follow‐up in early stage breast cancer

The aim of this research was to investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of programmed death 1/programmed death ligand 1 (PD‐1/PD‐L1), phosphatase and tensin homolog (PTEN), tumor infiltrating lymphocytes (TILs), and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC). A total of 97 EBC patients who underwent standard surgery were investigated. Expression of PD‐1/PD‐L1 and PTEN and the density of CD3⁺ TILs, CD8⁺ TILs, and CD163⁺ macrophages were evaluated by immunohistochemical analysis. The association between the immunologic factors and clinical outcome was statistically analyzed. The density of CD3⁺ TILs, CD8⁺ TILs, and CD163⁺ macrophages and non‐expression of PTEN was significantly higher in cases of triple negative breast cancer. CD8⁺ TIL density and CD8⁺/PD‐L1⁺ expression were predictive factors for disease‐free survival and overall survival (OS). Human epidermal growth factor 2 (HER2)‐positive patients with PTEN expression and luminal/HER2‐negative patients without PD‐L1 expression had significantly longer OS compared to patients without PTEN expression (P = 0.049) and with PD‐L1 expression (P = 0.036), respectively. Furthermore, patients with PD‐L1⁺/CD8⁺ expression had worse median progression‐free survival (P = 0.022) and median OS (P = 0.037) compared with patients without PD‐L1⁺/CD8⁺ expression. The CD3⁺ TILs, CD8⁺ TILs, and CD163⁺ macrophages were shown to infiltrate the tumor area of EBC. In particular, triple negative breast cancer had a higher rate of TIL infiltration within the tumor environment. Expression of PTEN and lack of PD‐L1 expression were associated with favorable survival in HER2‐positive and luminal/HER2‐negative EBC patients, respectively. The PD‐L1 expression combined with CD8⁺ density was significantly associated with an aggressive clinical outcome.     

Changes in aberrant DNA methylation after Helicobacter pylori eradication: A long‐term follow‐up study

Changes of DNA methylation in gastric mucosae after eradication of Helicobacter pylori have not been clarified yet. From this background, we investigated time course of DNA methylation following H. pylori eradication in 221 successfully H. pylori eradicated subjects with endoscopic follow‐up at least for 6 months, including 114 controls, 53 subjects with gastric dysplasia and 54 patients with early gastric cancer. All dysplasia and gastric cancer patients underwent endoscopic resection at the time of enrollment. The methylation levels in LOX, APC and MOS genes from noncancerous gastric mucosae using quantitative methylation‐specific PCR, as well as the histologic findings of gastric mucosae, were compared before and after eradication. Average follow‐up duration was 26.0 months (range: 6 to 76 months). H. pylori eradication decreased methylation levels in LOX (p‐value for slope < 0.001) but not in APC. In MOS, decrease of its methylation level following H. pylori eradication was significant among controls without intestinal metaplasia (IM) (p‐value for slope < 0.05); however, it was not observed among patients with IM or those with dysplasia or gastric cancer. After H. pylori eradication, methylation level in MOS persistently increased in patients with dysplasia or gastric cancer (p < 0.01). In conclusion, H. pylori eradication decreases aberrant DNA methylation with gene‐specific manner. Methylation level in MOS is associated with IM and may be used as a surrogate marker for gastric cancer risk, regardless of H. pylori eradication history.     

Increased risk of colorectal cancer among patients with biliary tract inflammation: A 5‐year follow‐up study

The purpose of the study was to investigate the risk of colorectal cancer among patients with biliary tract inflammation (BTI) compared to non‐BTI patients during a 5‐year follow‐up period. The study group comprised 1,613 patients with BTI, among which 32 cases (1.98%) developed colorectal cancer. The comparison group included 8,065 randomly selected subjects (5 for every patient with BTI), 74 of whom contracted colorectal cancer (0.92%). Stratified Cox proportional hazard regressions were calculated to estimate the adjusted hazard of colorectal cancer between the study group and comparison group. The adjusted hazard ratio for colorectal cancer for patients with BTI was 6.54 times (95% CI = 3.07–13.92) as high as for those without BTI within a 1‐year follow‐up period, 3.20 times (95% CI = 1.93–5.30) as high within a 3‐year follow‐up period, and 2.21 times (95% CI = 1.45–3.37) as high within a 5‐year follow‐up period. We also found that the adjusted hazard ratio for colorectal cancer for those with bile duct inflammation was 3.30 times (95% CI = 1.87–5.84) as high as for those without BTI within the 5‐year follow‐up period. However, no increased hazard of colorectal cancer was observed for patients with gallbladder inflammation. We concluded that patients with BTI had a significantly higher risk of colorectal cancer compared to patients without BTI.     

Prognostic value of p16‐INK4A protein in women with negative or CIN1 histology result: A follow‐up study

P16‐INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high‐grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy‐guided biopsy were included in the study; women surgically treated or having a CIN2–3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow‐up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16‐negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19–75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7–17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3–14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6–47.5). P16 overexpression is a good candidate for modulating follow‐up intensity after a negative colposcopy but is limited by its low prospective sensitivity.     

Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population‐based cohort study

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60–2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90–1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20–54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship.     

Cancer incidence and mortality: A cohort study in China, 2008–2013

The National Central Cancer Registry of China (NCCR) was the only available source of cancer monitoring in China, even though only about 70% of cancer registration sites were qualified by now. In this study, based on a national large prospective cohort‐the China Kadoorie Biobank (CKB), we aimed to provide additional cancer statistics and compare the difference of cancer burden between urban and rural areas of China. A total of 497,693 cancer‐free participants aged 35–74 years were recruited and successfully followed up from 2004 to 2013 in 5 urban and 5 rural areas across China. Except for traditional registration systems, the national health insurance system and active follow‐up were used to determine new cancer incidents and related deaths. The mortality‐to‐incidence ratio (MIR) was used to compare the differences of cancer burden between urban and rural areas of China. We found that cancer mortality coincided well between our cohort and NCCR, while the incidence was much higher in our cohort. Based on CKB, we found the MIR of all cancers was 0.54 in rural areas, which was approximately one‐third higher than that in urban areas with 0.39. Cancer profiles in urban areas were transiting to Western distributions, which were characterized with high incidences of breast cancer and colorectal cancer; while cancers of the esophagus, liver and cervix uteri were still common in rural areas of China. Our results provide additional cancer statistics of China and demonstrate the differences of cancer burden between urban and rural areas of China.