Subsequent Primary Cancers Research Articles

Cancer Risk Factors Among Adults with Serious Mental Illness

Background There is strong evidence to suggest that adults living with serious mental illness have a higher risk of mortality and morbidity than the general U.S. population, including a higher risk of mortality associated with certain cancers and cancer-related deaths. The potential loss of life expectancy among this population may be as high as 25 years compared to those without a mental illness. There are numerous challenges faced by people with serious mental illness, and behavioral factors that may contribute to increased cancer risk, including high prevalence of smoking, obesity, physical inactivity, substance abuse, and infectious diseases. Many of these individuals are uninsured, homeless, have a dual diagnosis of substance abuse, and are least likely to access and use preventive healthcare services. There is growing concern that those with serious mental illness experience disparities in health education, health prevention services, cancer screening, access to diagnostic testing, cancer case recognition, and higher cancer case fatalities. Although there are many interrelated and complex factors associated with cancer-related risk among this vulnerable population, many of these factors can be addressed. This paper aims to increase awareness of cancer risk factors and implications of employing innovative health promotion and cancer-prevention strategies among people with serious mental illness.

Tobacco smoking and the risk of subsequent primary cancer among cancer survivors: a retrospective cohort study

BackgroundSmoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. Patients and methodsIn total, 29 795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression. ResultsEver smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites. ConclusionsThese findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.

Germline BAX Deletion in a Patient With Melanoma and Gastrointestinal Stromal Tumor

isinvolved in those syndromes, it must be a rare event. A ccording to a population-based registry udst y ( 8 ) ~ 12 % paof tients wih melat noma develop one or more subsequent pri-mary cancers, most frequently another melanoma, female breast cancer, pros-tate cancer, or non-Hodgkin lymphoma. Soft tissue sarcomas are also signi fi cantly increased. However, the co-occurrence of GIST and melanoma in the same patient is an unusual fi nding; there are only three reports in the literature, but unfortunately genetic investigation was not performed in any of them ( 9 – 11 ). GIST is a rare tumor ht at accounts or f < 1 % of all gastroin-testinal malignancies and derives from mesenchymal / stromal cells driven by onco-genic activation of

Lipid Metabolism Genes in Contralateral Unaffected Breast and Estrogen Receptor Status of Breast Cancer

Risk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer would aid the development and implementation of distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk because women with ER-negative (ER-) index primaries are at high risk for subsequent ER-negative primary cancers. We conducted random fine needle aspiration of the unaffected breasts of cases. Samples from 30 subjects [15 ER-positive (ER+) and 15 ER- cases matched for age, race and menopausal status] were used for Illumina expression array analysis. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples. A validation set consisting of 36 subjects (12 ER+, 12 ER- and 12 standard-risk healthy controls) was used to compare gene expression across groups. ER- case samples displayed significantly higher expression of 18 genes/transcripts, 8 of which were associated with lipid metabolism on gene ontology analysis (GO: 0006629). This pattern was confirmed by qRT-PCR in the same samples, and in the 24 cases of the validation set. When compared to the healthy controls in the validation set, significant overexpression of 4 genes (DHRS2, HMGCS2, HPGD and ACSL3) was observed in ER- cases, with significantly lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. These data suggest that differential expression of lipid metabolism genes may be involved in the risk for subtypes of breast cancer, and are potential biomarkers of ER-specific breast cancer risk.

Risk of subsequent primary cancer among prostate cancer patients in Bavaria, Germany

As the prevalence of prostate cancer in Germany is increasing, the issue of subsequent primary cancer (SPC) becomes more relevant. The aim of this study was to estimate the risk and its changes over time of developing SPC among prostate cancer patients compared with the general male population in Bavaria, southern Germany. Utilizing data from the Population-Based Cancer Registry Bavaria, the risk of SPC was evaluated in 59 259 men with prostate cancer diagnosed between 2002 and 2008 who contributed 159 892 person-years. The relative and absolute risk of developing SPC were calculated using the standardized incidence ratio (SIR) and the excess absolute risk. Changes in the risk were examined by plotting the SIR and its 95% confidence interval against time after the diagnosis of prostate cancer. The overall risk of SPC was significantly increased by 14% compared with the general male population. With regard to specific cancer types, a significantly increased risk of SPC was found for the urinary bladder, kidney, pancreas, melanoma of skin, leukemia, myeloma, brain/nervous system, renal pelvis/ureter, thyroid, and the small intestine. The absolute risk of SPC for most cancer types, however, was below 10 cases per 10 000 person-years. A significantly decreased risk of SPC was found in the lung/bronchus and the liver. Although detection bias cannot be excluded as a contributing factor for our results, we recommend continuing follow-up care of prostate cancer patients particularly with respect to SPC of the urinary system as a precaution.

Early central airways lung cancer

Early central airways lung cancer accounts for very small percentage of all lung cancers. Given this fact, it is much difficult to carry out a prospective randomized comparative clinical trial. Even retrospective studies can offer important information. Early central airways lung cancer is usually detected by sputum cytology. If sputum cytology shows atypical epithelial cells implying malignancy, the next thing we have to do is bronchoscopy. Both autofluorescence bronchoscopy and white light bronchoscopy were superior to white light bronchoscopy alone in detecting this type of lung cancer. Natural history of this cancer showed about the two-thirds of the patients die from original disease within 10years. If the tumor length is 10mm or less, photodynamic therapy is a first-line modality. After photodynamic therapy, a 5-year overall survival of about 80% and a 10-year overall survival of 70% can be expected. If a cancer does not meet the criteria for photodynamic therapy, surgical resection is recommended, and 5-year overall survival of about 80% can be expected. Segmentectomy should be considered because of pulmonary function preservation if a tumor is located at segmental bronchi or beyond it. The frequency of multicentricity is high. Treatment strategy for subsequent primary lung cancer is an important key for the prognosis of patients with treated early central airways lung cancer. Surgical resection is still the most reliable treatment of subsequent primary lung cancer, except for in situ or microinvasive carcinoma located centrally, which could be cured by photodynamic therapy.

Risk of tobacco-related multiple primary cancers in Bavaria, Germany

BackgroundWith the prospect of increasing prevalence of cancer, the issue of multiple primary cancers becomes more relevant. The aim of this study was to estimate the risk of developing a tobacco-related subsequent primary cancer (TRSPC) in persons with a tobacco-related first primary cancer (TRFPC) compared with the general population in Bavaria, Germany.MethodsUsing data from the Population-Based Cancer Registry Bavaria, we analyzed TRFPC and TRSPC diagnosed in Bavaria between 2002 and 2008 to estimate the relative and absolute risk of developing TRSPC using standardized incidence ratios (SIR) and excess absolute risks (EAR).Results121,631 TRFPC in men and 75,886 respective cancers in women were registered, which in 2.5% of male and 1.2% of female cancer patients were followed by at least one TRSPC. In both males and females, the highest increased risks compared to the general population were found within the group of cancer in the mouth/pharynx, oesophagus, larynx, and lung/bronchus.ConclusionsWith respect to cancer in the mouth/pharynx, oesophagus, larynx, lung/bronchus, kidney, urinary bladder and urinary tract, smoking was confirmed as a shared risk factor based on our finding of mutually significantly increased risks of TRSPC. The results of this study illustrate the importance of smoking cessation and of continued follow-up care especially of smokers with the aforementioned TRFPC to detect TRSPC at an early stage.

Systematic research relating to the follow-up of survivors of cancer when young in the UK: methods and selected results

The British Childhood Cancer Survivor Study (BCCSS) comprises 18,000 individuals diagnosed with cancer before aged 15 years, between 1940 and 1991, in Britain, who survived at least 5 years from diagnosis. This will be extended to eventually include 40,000 5-year survivors of childhood cancers diagnosed between 1940 and 2010 in Britain. Studies of late mortality, subsequent primary cancers and non-neoplastic morbidity are undertaken using national registries for death and cancer, questionnaire surveys and linkage to hospital episode statistics (for publications see www.bccss.bham.ac.uk). The Teenage and Young Adult Cancer Survivor Study comprises 300,000 individuals diagnosed with cancer when aged 15 to 39 years, in England and Wales, between 1971 and 2006; 170,000 survived at least 5 years from diagnosis and will be investigated using methodology used in the BCCSS. The BCCSS will contribute towards the PanCareSurFup a 5-year programme grant funded by the European Commission and involving most European countries. Such large population-based investigations produce reliable, unbiased and comprehensive evidence providing a rational basis for many clinical and policy decisions.

Risk of Subsequent Primary Thyroid Cancer after Another Malignancy: Latency Trends in a Population-based Study

To evaluate the risk of a subsequent primary thyroid cancer (SPTC) in patients with common invasive cancers, with attention to latency trends and histology associations. Patients with one of 10 common invasive cancers were followed from 1975 to 2008 in 9 registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratios (SIRs) for SPTC were determined by the multiple primary-SIR program in SEER*Stat. A total of 2502 SPTCs were observed. Greatly elevated SIRs for SPTC were noted for 9 of 10 evaluated cancers in the 12 months after initial diagnosis. The SIRs remained elevated 12-59 months after diagnosis for all cancers except leukemia, uterine, and bladder cancers. Increased risks persisted 60-119 months beyond diagnosis for renal (SIR 2.56) and breast cancer (SIR 1.16); and 120+ months for renal cancer (SIR 2.46). Increased SPTC risk after renal and female breast cancers was mostly seen in nonirradiated patients. The principal histology association was between papillary thyroid cancer and renal cell carcinomas. Many common cancers are associated with increased risk of SPTC beyond 12 months of initial diagnosis. Although this can be explained partly by continued surveillance bias, radiation effects, and known rare familial associations for some tumors, these factors alone are unlikely to explain the persistent, significant two-way association with renal and breast cancers. Additional research is needed to further define the biological and environmental mechanisms underlying these associations.

Long-Term Survival in Young Women: Hazards and Competing Risks after Thyroid Cancer

Background. Differentiated thyroid cancers (DTCs) are one of the most common and survivable cancers diagnosed in women. We examine factors associated with long-term survival and competing risks of death in women diagnosed with DTC under the age of 40 (<40) and aged 40 and older (40+). Methods. SEER data was used to identify DTCs diagnosed in women from 1975 to 2009. We examined overall (OS), disease-specific (DSS), other cancer (OCS), and non-cancer-related (NCS) survival using multivariate Cox proportional hazards modeling. Results. Observed survival was 97.2% for <40 (n = 14,540) and 82.5% for 40+ (n = 20,513). Distant stage (HR = 1.96, 95% CI 1.23–3.07), non-Hispanic Black (HR = 2.04, 95% CI 1.45–2.87), being unmarried (HR = 1.26, 95% 1.03–1.54), and subsequent primary cancers (HR = 4.63, 95% CI 3.76–5.71) were significant for OS in women <40. Age was an effect modifier for all survival outcomes. Racial disparities in NCS were most pronounced for young non-Hispanic black women (HR = 3.36, 95% CI 2.17–5.22). Women in both age groups were more likely to die from other causes. Conclusions. Age at diagnosis remains one of the strongest prognostic factors for thyroid cancer survival. More directed efforts to ensure effective care for comorbid conditions are needed to reduce mortality from other causes.

Variation in the risk of radiation-related contralateral breast cancer by histology and estrogen receptor expression in SEER

Radiation exposure, particularly at a young age, is an established cause of breast cancer. It is not known whether radiation-related breast cancer risk varies by molecular subtype. We characterized the relative risk (RR) of contralateral breast cancer (CBC) related to radiotherapy by histology and estrogen receptor (ER) status of the CBC in five-year survivors in the Surveillance, Epidemiology, and End Results database using Poisson regression models adjusted for attained age and calendar year, age at and year of treatment, ER status of the first breast cancer, and disease stage. 205,316 female breast cancer survivors were followed for an average of 10years from 1973 until 2007, during which time 6924 women developed a subsequent primary invasive breast cancer in the contralateral breast. The overall RR (and 95% confidence interval (CI)) of radiotherapy-related CBC was 1.11 (1.05-1.16). There was no heterogeneity in risk according to histology of the CBC (P>0.50) for all ages or young age at exposure, but case numbers were small for subtypes other than ductal and lobular carcinomas. Information on ER status was available from 1990 onwards for 3546 CBC cases, of which 2597 (73%) were ER+and 949 (27%) were ER-. The RRs were 1.10 (1.02-1.19) for ER+CBC and 1.19 (1.04-1.35) for ER-CBC (P (difference)=0.33). Among women treated age<35years, radiation-related risk of CBC was non-significantly elevated for ER- (RR=1.38, 95% CI: 0.96-1.97) but not for ER+tumors (RR=0.80, 95% CI: 0.47-1.35) (P (difference)=0.09). We did not find clear evidence that radiation-related risk varies by histology or ER status, but our findings, which were the first to examine this question, were suggestive of possible differences by ER status that may merit further investigation.

Subsequent primary cancers among men and women with in situ and invasive melanoma of the skin

An estimated 750,000 melanoma survivors in the United States are at increased risk of subsequent primary cancers. We sought to assess the risk of developing subsequent primary cancers among people with cutaneous melanoma. Using 1992 to 2006 data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program, 40,881 people with in situ melanoma and 76,041 people with invasive melanoma were followed up (mean of 5.6 years) for the development of subsequent primary cancers. The observed number of subsequent cancers was compared with those expected based on age-/race-/year-/site-specific rates in the Surveillance, Epidemiology, and End Results population. Standardized incidence ratios (SIRs) (SIR = observed number/expected number) were considered statistically significant if they differed from 1, with an alpha level of 0.05. After a first primary in situ melanoma, risk was significantly elevated for subsequent invasive melanoma and chronic lymphocytic leukemia among men (SIRs = 8.43 and 1.44, respectively) and women (SIRs = 12.33 and 1.79, respectively). After a first primary invasive melanoma, risk was significantly elevated for subsequent invasive melanoma, thyroid cancer, non-Hodgkin lymphoma, and chronic lymphocytic leukemia among both men (SIRs = 12.50, 2.67, 1.56, and 1.57, respectively) and women (SIRs = 15.67, 1.77, 1.42, and 1.63, respectively). Case ascertainment issues particularly affecting in situ melanoma cases could affect results. The role of detection bias in the diagnoses of some subsequent cancers cannot be completely eliminated. The findings of the study should guide the development of strategies such as posttreatment surveillance, screening, and ultraviolet exposure education among melanoma survivors to improve cancer survivorship.

Risk of Anal Cancer in a Cohort With Human Papillomavirus–Related Gynecologic Neoplasm

To assess the development of anal cancer in women diagnosed with a human papillomavirus-related cervical, vulvar, or vaginal neoplasm. Using data from National Cancer Institute's Surveillance, Epidemiology and End Results program from 1973 through 2007, 189,206 cases with either in situ or invasive cervical, vulvar, or vaginal neoplasm were followed for 138,553,519 person-years for the development of subsequent primary anal cancer. Standardized incidence ratios were calculated from the observed number of subsequent anal cancers compared with those expected based on age-, race-, and calendar year-specific rates in the nonaffected population. Anal cancer developed in 255 women with a history of in situ or invasive gynecologic neoplasm, aggregate standardized incidence ratio of 13.6 (95% confidence interval [CI] 11.9-15.3), indicating a 13-fold increase in anal cancer compared with expected. The standardized incidence ratio for anal cancer incidence among women with in situ vulvar cancer was 22.2 (95% CI 16.7-28.4) and was 17.4 (95% CI 11.5-24.4) for those with invasive vulvar cancer. The standardized incidence ratio for anal cancer incidence in women with in situ cervical cancer was 16.4 (95% CI 13.7-19.2) and was 6.2 (95% CI 4.1-8.7) for women with invasive cervical cancer. The standardized incidence ratio for anal cancer incidence among women with in situ vaginal cancer was 7.6 (95% CI 2.4-15.6) and was 1.8 (95% CI 0.2-5.3) for invasive vaginal cancer. Women with human papillomavirus-related gynecologic neoplasm are at higher risk for developing anal cancer compared with the general population. This high-risk population may benefit from close observation and screening for anal cancer.

Long-Term Survival Among Patients With Hodgkin's Lymphoma Who Developed Breast Cancer: A Population-Based Study

The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC. For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002). Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted.

Characteristics and survival associated with ovarian cancer diagnosed as first cancer and ovarian cancer diagnosed subsequent to a previous cancer

Objective: To examine the risk of subsequent primary ovarian cancer among women diagnosed previously with cancer (subsequent cohort) and to compare demographic and tumor characteristics affecting overall survival of these women and women diagnosed with first primary ovarian cancer (index cohort). Methods: We identified the two cohorts of women using the 1973–2005 Surveillance, Epidemiology and End Results (SEER) result data. We calculated relative risk of subsequent primary ovarian cancer and estimated 5-year risks of dying (hazard-ratios) after diagnosis of the first or subsequent primary ovarian cancer in the two cohorts, respectively using Cox modeling. Results: Women diagnosed with index cancers of the corpus uteri, colon, cervix, and melanoma at age younger than 50 had increased risk of ovarian cancer within 5 years after diagnosis ( p < 0.05); young breast cancer survivors had continued risk beyond 20 years. In 5-year follow-up survival analysis, the factors associated with a better survival ( p < 0.05) were similar in both cohorts and included more recent diagnosis; localized or regional disease; age <50 years at diagnosis; and being white versus black. A lower risk of dying from mucinous, endometrioid, or non-epithelial tumors than from serous was seen after 15 months ( p < 0.01), or after 32 months from diagnosis of the index and subsequent cohorts, respectively. Conclusions: Age, stage, and histology affect ovarian cancer survival. The increased risk of ovarian cancer over time, especially among breast and colon cancer survivors who are less than 50 years of age, suggests common etiologies and necessitates careful surveillance by health care providers and increased survivors awareness through educational efforts.

Measuring the effect of including multiple cancers in survival analyses using data from the Canadian Cancer Registry

Background: In survival analyses using cancer registry data, second and subsequent primary cancers diagnosed in individuals are typically excluded. However, this approach may lead to biased comparisons of survival between cancer registries, or over time within a single registry. Purpose: To examine the impact of including multiple primary cancers in the derivation of survival estimates using data from a population-based national cancer registry. Methods: Five-year relative survival estimates for persons aged 15–99 years at diagnosis were derived using all eligible primary cases from the Canadian Cancer Registry (CCR)—a population-based registry containing information on cases diagnosed from 1992 onward—and then again using first primary cases only. Any pre-1992 cancer history of persons on the CCR was obtained by using auxiliary information. Results: The inclusion of multiple cancers resulted in lower estimates of 5-year relative survival for virtually all cancers studied. The effect was somewhat attenuated by age-standardization (e.g., from 1.3% to 1.0% for all cancers combined), and was greatest for bladder cancer (−2.4%) followed by oral cancer (−1.9%)—cancers that had the first and third lowest proportions of first cancers, respectively. For the majority of cancers the difference was less than 1.0%. Cancers for which there was virtually no difference (e.g., lung, pancreatic, ovarian and liver) tended to be those with a poor prognosis. Conclusion: Inclusion of second and subsequent primary cancers in the analysis tended to lower estimates of relative survival, the extent of which varied by cancer and age and depended in part on the proportion of first primary cancers.

Second primary cancers following borderline ovarian tumors

Several studies have reported an increased risk of second primary cancers subsequent to invasive epithelial ovarian cancer. However, there is no adequate data regarding such risk in borderline ovarian tumors (BOTs). The aim of this study was to evaluate the risk of subsequent second primary cancers among women with BOTs. BOT patients treated in our center between December 1985 and April 2009 were retrospectively screened for developing second primary cancer during follow-up period. There were 96 women diagnosed with BOT. Mean age at the time of diagnosis was 47 ± 14.3, ranging from 19 to 79. Eighty-eight (91.6%) patients had stage I disease, two patients (2.1%) had stage II and six (6.2%) had stage III. Twenty-five (26.0%) patients received platinum-based adjuvant chemotherapy. Mean follow-up time was 96.5 ± 442 months (range: 9-280 months). There were ten (10.4%) recurrences. Only one patient developed second primary cancer. Second primary cancer observed in this case was basal cell carsinoma of the eyelid, which was diagnosed 2 years after primary disease. There were no patients with common women's cancers such as breast and colorectal cancers. These findings do not suggest increased risk of subsequent cancers in patients with BOT. However, population-based studies are needed for evaluating exact risk of developing second primary malignancies in women with BOTs.

A breast cancer prognostic signature predicts clinical outcomes in multiple tumor types

Epidemiological studies indicate an increased risk of subsequent primary ovarian cancer from women with breast cancer. We have recently identified a 28-gene expression signature that predicts, with high accuracy, the clinical course in a large population of breast cancer patients. This prognostic gene signature also accurately predicts response to chemotherapy commonly used for treating breast cancer, including CMF, Tamoxifen, Paclitaxel, Docetaxel and Doxorubicin (Adriamycin), in a panel of 60 cancer cell lines of nine different tissue origins. This prompted us to investigate whether this prognostic gene signature could also predict clinical outcome in other cancer types of epithelial origins, including ovarian cancer (n=124), colon tumors (n=74) and lung adenocarcinomas (n=442). The results show that the gene expression signature contributes significantly more accurate (P<0.05; compared with random prediction) prognostic information in multiple cancer types independent of established clinical parameters. Furthermore, the functional pathway analysis with curated database delineated a biological network with tight connections between the signature genes and numerous well established cancer hallmarks, indicating important roles of this prognostic gene signature in tumor genesis and progression.

Long-term survival among 298 Hodgkin lymphoma (HL) patients who develop breast cancer (BC): A population-based study.

1502 Background: The markedly increased risk of BC among women receiving chest radiotherapy for HL is well established. However, no large, population-based studies exist that describe overall survival (OS) and cause-specific survival (CSS) compared to women with a first primary BC. Methods: For 298 HL survivors who developed BC (HL-BC patients) and 405,223 women with a first or only BC (BC-1 patients), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. Results: Compared with BC-1 patients, the HL-BC group was significantly younger at BC diagnosis (p < 0.0001), had a greater likelihood of high grade BC (p > 0.02), and greater likelihood of estrogen negative BC (p < 0.004) and progesterone receptor negative BC (p > 0.005 for localized BC and p > 0.06 for regional BC). HL-BC patients were > 1.5 times (p < 0.0001) more likely to undergo mastectomy (rather than breast conserving surgery) compared with BC-1 pts, and were > 2 times (p < 0.0001) less likely to have received radiation than BC-1 patients. Fifteen-year OS among HL-BC patients was significantly inferior to BC-1 patients: 48% versus 69% respectively (p<0.0001) for localized BC, and 33% versus 43% (p < 0.0001) for regional/distant BC. HL-BC patients had a significantly increased 7-fold risk (p < 0.0001) of death from other cancers (i.e., not HL or BC) compared to BC-1 patients. Mortality due to heart disease among HL-BC patients with either localized or regional/distant disease was also significantly increased (hazard ratio 2.22, p > 0.04; and hazard ratio 4.28, p > 0.02 respectively) compared to BC-1 patients. While 10-year BC CSS was similar for HL-BC and BC-1 patients with regional/distant disease, it was inferior for patients with localized BC (82% versus 88% respectively (p > 0.002). Conclusions: Women with HL may survive a subsequent diagnosis of BC only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in HL-BC patients is warranted. No significant financial relationships to disclose.

Primär- und Sekundärprophylaxe von Hauttumoren nach Organtransplantation

Skin cancer constitutes the most frequently reported post-transplant malignancy in solid organ transplant recipients (OTR) worldwide. Whereas the risk for malignant melanoma is only moderately increased, non-melanoma skin cancers (NMSC) seem to thrive on chronic immunosuppression and account for up to 95% of post-transplant cutaneous malignancies. Compared to the general population cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AK) characteristically show even higher incidences than basal cell carcinoma (BCC) and act as an indicator for the development of multiple primary cutaneous neoplasias and locally recurrent cancers (field cancerization). Early diagnosis and therapy of pre-malignant cutaneous lesions is crucial for the secondary prophylaxis of further invasive and highly aggressive skin cancers. High quality interdisciplinary care and prophylactic modalities, including consistent and sufficient UV protection, topical immunmodulatory therapies of UV-damaged skin areas, retinoid chemoprevention as well as tapering immunosuppressive treatment or the selection of immunosuppressants with proposed antiangiogenic properties like mTor-inhibitors may help to reduce the multiplicity of subsequent primary skin cancers in high-risk patients. Apart from the continuous need for educational intervention of OTR in the primary prophylaxis of post-transplant skin cancers, dermatologic care occupies a central position within the field of transplantation medicine in terms of pre- and post-transplantation dermatologic evaluation and therapy as well as the implication of timely and effective secondary preventive approaches in the management of this high-risk patient population.