Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population.

BACKGROUND: We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population. METHODS: We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses. RESULTS: Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients. CONCLUSIONS: Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.

Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations of Kentucky.

OBJECTIVES: The aim of this study was to investigate whether patients with lung cancer in Appalachian Kentucky are more likely to develop multiple primary cancers than patients in non-Appalachian Kentucky. Additional analyses were conducted to identify other factors that may be associated with an increased hazard of developing multiple primary cancers in patients with lung cancer. METHODS: The data for this retrospective, population-based cohort study of 26,456 primary lung cancer patients were drawn from the Kentucky Cancer Registry. For inclusion in the study, patients must have been diagnosed between January 1, 2000 and December 31, 2013 and they must either have continually resided in Appalachian Kentucky or continually resided in non-Appalachian Kentucky. Cases were excluded if the patient was diagnosed as having additional primary cancers within 3 months of the initial diagnosis of primary lung cancer. The medical records for each case were examined to determine whether the patient was subsequently diagnosed as having additional primary cancers. The Cox proportional hazards model was then used to assess whether there was an association between the region in which the patients live and the likelihood of developing multiple primary cancers. Time to event was considered as the time from diagnosis to either death or development of a second primary cancer. RESULTS: The results presented here indicate that the risk of developing multiple primary cancers is the same for patients with lung cancer throughout Kentucky (hazard ratio [HR] 1.002, P = 0.9713). We found no evidence for a greater hazard in patients from Appalachia; however, additional analyses revealed several high-risk groups. Male patients and older patients had a significantly greater hazard of developing multiple primary cancers (HR 1.169, P = 0.012 and 1.015, P = 0.0001, respectively). In addition, patients who underwent surgery and those who were diagnosed initially as having an earlier stage of cancer also were more likely to develop multiple primary cancers (HR 1.446, P = 0.0003 and 0.684, P = 0.0015, respectively). CONCLUSIONS: This is a negative study. Patients with primary lung cancer living in Appalachian Kentucky are not at a greater risk of developing multiple primary cancers than those residing in non-Appalachian Kentucky. High-risk groups identified in this study are male patients and older patients. The increased hazard seen in patients who underwent surgery or those who were diagnosed as having earlier stages of lung cancer are likely an artifact of these patients living longer and, therefore, having more time to develop additional primary cancers.

[C-KIT in gastrointestinal stromal tumors and associated malignancies: A Study in a population with genetic isolation]. / C-kit en tumores estromales gastrointestinales y neoplasias asociadas: estudio en población con aislamiento genético.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Numerous studies have reported the association between GIST and other neoplasms. OBJECTIVES: The aim of this study was to investigate the possible association between GIST and other tumors in a genetically isolated population. METHODS: A retrospective study was conducted of patients with GIST between 2002 and 2009 at our center. Epidemiological, pathological and family data in patients with GIST alone (group A) were compared with those in patients with GIST associated with other neoplasms (group B). A possible common genetic mechanism was investigated between GIST and associated malignancies by testing the detection of the immunohistochemical marker, CD117, in all tumors. RESULTS: Twenty-two patients with GIST were identified, 10 in group A (45%) and 12 in group B (55%). In group B, the associated tumor was malignant in 6 patients (50%) and benign in another 6 (50%). Of the 22 patients with GIST, 8 (36%) had a family history of malignancies. Of these 8 patients, 7 (87.5%) were in group B (p=0.03) and 3 (37.5%) showed the same pathological type of neoplasm as their relatives. All GIST were positive for CD117 whereas associated malignancies were negative for this marker. CONCLUSION: We did not find immunohistochemical positivity for CD117 in malignancies associated with GIST. Given the special characteristics of the study population, the association between GIST and associated malignancies may be incidental.

Basal cell carcinoma in Singapore: a prospective study on epidemiology and clinicopathological characteristics with a secondary comparative analysis between Singaporean Chinese and Caucasian patients.

BACKGROUND/OBJECTIVES: Susceptibility to and clinical presentation of basal cell carcinoma (BCC) differ in Asian and Caucasian populations. This study aims to evaluate the epidemiological and clinicopathological characteristics of BCC in a multiracial Singaporean population, with a secondary comparative analysis between Chinese and Caucasian patients. METHODS: We prospectively studied patients with newly diagnosed, histologically confirmed BCC at the National Skin Centre, Singapore from 2004 to 2008. RESULTS: In total, 274 BCC from 260 patients were studied, with 19 patients having two or more tumours. Their mean age was 67.5 years and 54% were male. Chinese comprised 80% and Caucasians 14%. The Chinese were 1.8-fold as likely as Caucasians to be older than 60 years, and experienced itch thrice more frequently. Caucasians developed multiple BCC threefold and truncal or upper limb BCC 2.9-fold more frequently than the Chinese. In terms of tumour subtype, morphoeic BCC was 2.7-fold more common in Caucasians. Pigmented BCC occurred 2.7-fold more often in the Chinese, most frequently on the head and neck of elderly Chinese. CONCLUSIONS: Compared to the Chinese, BCC occurred more often in younger Caucasians, with a predilection for the trunk and upper limb, suggesting a greater role for recreational sun exposure as a risk factor. Pigmented BCC more commonly occurred on the head and neck of elderly Chinese and may be reflective of cumulative sun exposure as a risk factor. Aggressive morphoeic BCC was more common in Caucasians than in Singaporean Chinese patients.

[Epidemiological and clinical characteristics of primary ocular cancers in blacks: our experience with 111 cases]. / Aspects épidémiologiques et cliniques des cancers oculaires primitifs du mélanoderme : notre expérience à propos de 111 cas.

INTRODUCTION: In this work, the authors aim to study clinical and epidemiological characteristics of ocular and orbital primary cancers in sub-Saharan African. PATIENTS AND METHODS: This is a retrospective study over a period of 21 years, from 1984 to 2004, including all cases of ocular cancer, histologically proven after surgery of the globe or the orbit. For each patient, we studied the following parameters: age, sex, reason(s) for consultation, the affected eye, and histological result of the operative specimen. These data were collected by studying the departmental surgical registry, patient medical records and the tumor registry of the anatomicopathology laboratory of a tertiary care hospital in sub-Saharan Africa. RESULTS: We collected data on 111 black patients, among whom 15 cases (13.5%) presented with bilateral involvement, for a total of 126 eyes. The sex ratio was 1.17. Presenting signs showed a predominance of leukocoria (30.2%) followed by proptosis (21.7%) and in third place, protruding conjunctival mass (10.8%). Retinoblastoma was found most frequently, representing 66.6% of the oculo-orbital tumors and 95.45% of the tumors of the globe; followed by epidermoid carcinoma, representing 15.08% of cases. Malignant melanoma was third most common, representing 4.76%, with 83% arising in the anterior uvea and 7% in the choroid. Basal cell carcinoma and rhabdomyosarcoma follow in fourth place. Basal cell carcinoma constituted half (50%) of the eyelid tumors. Rhabdomyosarcoma was the most common orbital tumor in our series (57%). Next were lymphomas with conjunctival localization (2.38%), acute leukemia with orbital localization (1.59%) and rare tumors, palpebral dermatofibrosarcoma (0.79%), an orbital angiosarcoma (0.79%), a glioblastoma of the globe (0.79%) and a malignant solitary fibrous tumor of the orbit (0.79%). CONCLUSION: Ocular and orbital primary cancers in blacks remain tumors of the young, equally distributed between the sexes. Retinoblastoma is the most frequent, followed by epidermoid carcinoma. The globe is the preferential localization of these cancers.

Genotype analysis in Hungarian patients with multiple primary melanoma.

Multiple primary melanoma patients (MPMps) have better prognosis and are more prone to genetic predisposition than single melanoma patients. We aimed to compare genetic background (CDKN2A, CDK4, MITF, MC1R) of 43 Hungarian MPMps with their clinicopathological data. We observed a higher rate of synchronous first and second melanoma (MM) (49%) and a higher frequency of non-melanoma tumor co-occurrence (42%) than reported previously. CDKN2A mutation frequency was 4.7% (E69G, R99P). We identified a new human MC1R variant (D117G) and reported MC1R variant distributions in Hungarian MMs for the first time. The rare R163Q was exceptionally common among Hungarian MPMps, a variant otherwise frequent in Asia, but not in Europe. MC1R 'R' carriers showed histopathological signs of a more progressive disease than 'r' carriers did; however, tumor-infiltrating lymphocytes (TILs) in their second melanomas occurred significantly more frequently. Calculating 5-year overall survival, 'R' carriers showed more unfavourable prognosis (87%) than 'r' carriers did (95%).

Case-control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk.

Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg(213)His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case-control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens.

Multifocal desmoplastic medulloblastoma in an african-american child with nevoid basal cell carcinoma (gorlin) syndrome. Case report.

The authors present the case of a 2.5-year-old African-American boy with desmoplastic medulloblastoma (MB) and nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, an autosomal dominant disorder resulting from mutations in the patched (PTCH) gene that predisposes to neoplasias (including basal cell carcinomas [BCCs] and MB) and to widespread congenital malformations. The diagnosis of NBCCS was suspected based on the clinical examination, patient and family medical histories, and histopathological characteristics of the tumor. Radiotherapy was withheld. The diagnosis of NBCCS was confirmed by DNA testing, which revealed a novel mutation in the PTCH gene. This is the first report of an African-American child with MB diagnosed with NBCCS prior to radiotherapy. Although only a small number of patients with MB have NBCCS, the diagnosis must be considered because radiotherapy in such patients can lead to the formation of BCCs and other intracranial neoplasms within the irradiated field. This case emphasizes the importance of obtaining thorough family and patient medical histories and of carefully examining the patient and close relatives for signs of NBCCS to avoid the potentially devastating consequences of missing this diagnosis.

Colorectal cancer in Asians: a demographic and anatomic survey in Malaysian patients undergoing colonoscopy.

BACKGROUND: Colorectal cancer is one of the most common forms of gastrointestinal cancer in the world today. In the Asia-Pacific area, it is the fastest emerging gastrointestinal cancer. AIM: To determine the basic demographic features of patients with colorectal cancer and the anatomic distribution and characteristics of the tumour in a local Asian population. METHODS: We conducted a review of consecutive patients who had undergone colonoscopy from 1999 to 2003 at the University of Malaya Medical Center, Kuala Lumpur, Malaysia. RESULTS: Analysis was carried out on 3404 patients who underwent colonoscopy. A total of 228 patients (7%) were diagnosed with carcinoma. The mean age of diagnosis (+/-s.d.) was 64.4 +/- 13.1 years. The male to female ratio was 1.15. Polyps were noted in 470 patients (14%). Polyps detected concomitantly with a colorectal cancer were noted in 55 patients (2%). Four patients (0.1%) were diagnosed to have familial adenomatous polyposis coli. Of the 228 patients 209 (92%) had tumours at only one site whereas 19 (8%) had synchronous lesions. Tumours were mainly left sided [198 of 248 patients (80%)] with the majority located in the recto-sigmoid region. Detailed records of treatment were available only in 176 patients. A total of 147 of 176 patients (84%) underwent surgery and 50 (28%) also received adjuvant or palliative chemotherapy (28%). Seven of 154 patients (5%) were diagnosed to have stage A cancers, 64 (42%), stage B, 23 (15%), stage C and 60 (39%), stage D. Multivariate analysis using multiple logistic regression analysis showed that age > or =65 years (OR = 1.78; 95% CI: 1.35- 2.36) and Malay (OR = 2.09; 95% CI: 1.30-3.35) and Chinese (OR = 1.77; 95% CI: 1.77-2.69) race were significant independent predictive factors for colorectal cancer. CONCLUSIONS: The demography of colorectal cancer is different from western patients. Tumours were mainly left sided in our patients. However, no differences in anatomic location were found between races, men and women and younger and older age groups. Colorectal cancer presented in an advanced stage in the majority of patients.

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours.

To gain insight into the molecular mechanisms involved in the inherited predisposition to melanoma and associated neural system tumours, 42 Jewish, mainly Ashkenazi, melanoma families with or without neural system tumours were genotyped for germline point mutations and genomic deletions at the CDKN2A/ARF and CDK4 loci. CDKN2A/ARF deletion detection was performed using D9S1748, an intragenic microsatellite marker. Allele dosage at the p14ARF locus was analysed by quantitative real-time PCR employing a TaqMan probe that anneals specifically to exon 1beta of the p14ARF gene. For detecting point mutations, dHPLC and direct sequencing of the coding sequences of CDKN2A/ARF and CDK4 was used. No germline alterations in any of the tested genes were detected among the families under study. We conclude that in the majority of Ashkenazi Jewish families, the genes tested are unlikely to be implicated in the predisposition to melanoma and associated neural system tumours.

DNA repair and nonmelanoma skin cancer in Puerto Rican populations.

BACKGROUND: UV radiation is a risk factor for nonmelanoma skin cancer (NMSC). The relation between DNA damage and oncogenesis suggests that diminished DNA repair capacity (DRC) is involved in tumorigenesis. OBJECTIVE: The purpose of this study was to test the hypothesis that a low DRC is a susceptibility factor for the development of NMSC in Puerto Rico. METHODS: A case-control retrospective clinical study was done to compare the age-adjusted DRC in participants with and without NMSC. DRC was measured using a host cell reactivation assay with a luciferase reporter gene irradiated with UV light and transfected into human peripheral lymphocytes. An epidemiologic questionnaire was used to solicit risk factors. RESULTS: The mean (+/-2 SE) DRC of 177 control patients without skin cancer was 8.6% +/- 0.7. Participants (280) with NMSC had a 42% lower DRC (5.0% +/- 0.3). CONCLUSION: A low DRC is a susceptibility factor for NMSC.

Choroidal melanoma with oculodermal melanocytosis in Hispanic patients.

PURPOSE: To describe three Hispanic patients with oculodermal melanocytosis and uveal melanoma. METHOD: Case series. RESULTS: Three Hispanic patients with oculodermal melanocytosis and uveal melanoma underwent enucleation. The diagnosis of choroidal melanoma was confirmed by histopathologic examination. CONCLUSION: In the Hispanic population, uveal melanoma can occur in the presence of oculodermal melanocytosis.

BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer.

BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.

Nonmelanoma skin cancer in Japanese ethnic Hawaiians in Kauai, Hawaii: an incidence report.

BACKGROUND: Incidence reports of nonmelanoma skin cancer (NMSC) in Japanese persons are limited. Most studies have relied primarily on hospital records or voluntary reporting systems. OBJECTIVE: Our purpose was to determine the incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Bowen's disease (BD) in a defined Japanese population. METHODS: A prospective 5-year population-based incidence study was conducted on the island of Kauai, Hawaii from 1983 through 1987. RESULTS: Thirty Japanese Kauai residents, 12 men and 18 women, developed BCC during the 5-year study period. At the same time, 24 Japanese, 6 men and 18 women, were identified with SCC, and 11 had BD, three men and eight women. When standardized to the Japanese population in Japan, the annual BCC incidence rate was 30 per 100,000 Japanese Kauai residents with an average patient age of 75 years. More than 80% of these BCCs were localized to the head and neck. New BCCs developed in four patients with BCC, but none was a recurrence of a previously treated lesion. Five patients with BCC had SCC or BD concurrently or at other times. The SCC incidence was 23 per 100,000 Japanese Kauai residents with an average patient age of 80 years. The head and neck were again the most common anatomic sites. New SCCs subsequently occurred in two patients, in one of whom a localized recurrence also developed. Five patients with SCC had BCC simultaneously or at other times. The incidence of BD was 13 per 100,000 Japanese Kauai residents with an average patient age of 74 years. The extremities were the most common anatomic sites. One patient later had a new BD lesion and a recurrent BD lesion. Two patients had BCC or SCC at other times. CONCLUSION: We report incidence rates of BCC, SCC, and BD at least 45 times higher in the Japanese population in Kauai, Hawaii than rates for the Japanese population in Japan. Kauai's intense UV radiation and emphasis on outdoor activities may contribute. More Japanese women had NMSC than men, a sex difference not observed in Japan.

Survival differences between black and white women with breast cancer.

Several reports have indicated that black women with breast cancer have a poorer prognosis than white women. To investigate this phenomenon and to identify some of the underlying reasons, 172 patients with infiltrating ductal carcinoma of the breast, who were managed similarly, were studied. Survival analysis comparing the two populations with breast cancer revealed that white women had significantly longer overall survival (OS), P = 0.015 by Wilcoxon and 0.019 by log-rank, and borderline significantly longer disease-free survival (DFS), P = 0.04 by Wilcoxon and 0.07 by log-rank. While there was no significant difference in OS and DFS between the two groups with negative nodes, significantly poorer DFS and OS was noted in black patients with one to three positive lymph nodes compared to white patients, P = 0.008. The white patients had a higher incidence of hormone receptor-positive tumors, especially progesterone receptor (P = 0.0016). However, survival analysis failed to show any difference between the black and the white populations based on hormonal receptors. Such findings suggested that further investigation of other factor(s) is warranted.

Synchronous colorectal cancer in an Oriental population.

Thirty-four (4.1%) out of 820 patients operated for colorectal cancer between April 1989 and October 1992 were found to have synchronous cancers. Twenty (59%) were male and 14 (41%) were female. The mean age was 69.3 years (range = 25 to 89 yr). Synchronous tumours were located in the same or adjacent segments of the large intestine in 24 (71%) of the patients. A curative resection was performed in 27 (79%) patients, a palliative resection in 8 (18%) and one (3%) patient had a palliative colostomy only. Dukes' staging based on the worse of the 2 cancers showed 1 (3%) Dukes' A, 11 (32%) Dukes' B, 14 (38%) Dukes' C and 9 (27%) with disseminated disease. Age, sex and Dukes' staging did not differ significantly from those of patients with solitary cancers and prognosis was also not adversely affected.

Association between malignancies of the upper aerodigestive tract and uterine cervix.

Cancers of the cervix and buccal cavity share histologic, epidemiologic, and exposure characteristics. In particular, cigarette smoking and human papillomavirus (HPV) have been cited as etiologic cofactors of both malignancies. Using incidence data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute for the years 1973 through 1984, we evaluated the incidence of second cancers of the buccal cavity following an initial cervical cancer. Standardized incidence ratios (SIR) were uniformly elevated for both white (SIR = 2.0), and black (SIR = 3.5) women. There were also elevated risks for the development of cervical cancer following an initial buccal cavity cancer (SIRs = 3.3 and 2.5, respectively). A similar pattern was evident for laryngeal cancer among white women. HPV transmission could account in part for the paired occurrence of these two anatomically distinct cancer sites. Cigarette smoking could act as a synergistic cofactor in the malignant transformation of viral genome-harboring tissue.