Cancers Of Other Organs Research Articles

A case of early duodenal cancer observed during follow-up of intraductal papillary mucinous neoplasm

Duodenal cancer is a rare disease that accounts for 0.3％ of all primary gastrointestinal tract cancers. We report the case of an elderly patient diagnosed with and treated for early duodenal cancer detected during follow-up after resection of intraductal papillary mucinous neoplasm (IPMN). An 82-year-old man was diagnosed with IPMN during hospitalization for acute pancreatitis in 2004 and underwent pancreatic resection. In 2008, an elevated lesion measuring 15 mm in size was detected at the anterior wall of the duodenal bulb during gastroscopy. A mucosal lesion was also noted during endoscopic ultrasonography. Histopathological examination of a biopsy specimen identified well-differentiated adenocarcinoma. On the basis of these findings, endoscopic mucosal resection was performed. Although the tumor was resected in two parts, no residual malignancy was noted. Histopathological examination of the resected specimen revealed a 20×18 mm well-differentiated adenocarcinoma, pT1a (m), med, INF-α, ly (-), v (-), pHMx, pVM0. Gastrointestinal endoscopy performed two months after surgery and in 2013 did not show any obvious signs of tumor recurrence. IPMN is sometimes reported to occur in combination with cancers of other organs. However, to our knowledge this is the first case report of early duodenal cancer occurring in a patient with IPMN.

Frequency of multiple primary cancers in the lung and other organs in hemodialysis patients

We examined whether cancers frequently occur in hemodialysis patients, and therefore, investigated the features and outcomes of hemodialysis patients who had undergone surgery for non-small cell lung cancer. Between 1995 and 2011, 14 hemodialysis patients with lung cancer (8 males and 6 females) with a mean age of 67.0years successfully underwent pulmonary resection at our institution. We investigated the 5-year survival rate and causes of death. The occurrence of multiple primary cancers in our patients and other lung-cancer patients reported in the articles were statistically compared by Chi-square test. A p value <0.05 was considered to be statistically significant. The 5-year survival rate was 47.3%, and six patients had died before our investigation. Four of the six had died of non-cancerous diseases related to hemodialysis. Five of 14 patients had a history of other primary cancers in other organs, and this incidence rate of multiple primary cancers was significantly higher than in other lung-cancer patients (p=0.0071). The frequency of cancer in hemodialysis patients can be underestimated because of their early deaths by non-cancerous diseases. However, the incidence rate of multiple primary cancers may represent a unique characteristic of such patients.

Tu1696 Safety of Endoscopic Submucosal Dissection for Esophageal Cancer in Elderly Patients

Tu1696 Safety of Endoscopic Submucosal Dissection for Esophageal Cancer in Elderly Patients

The melanoma ‘epidemic’: lessons from prostate cancer

The rise in malignant melanoma incidence has been termed "epidemic". Closer scrutiny of epidemiologic data suggests overdiagnosis as the true cause of the dramatic rise in melanoma incidence. In epidemiologic terms, "overdiagnosis" describes lesions that are histologically malignant but biologically benign. Overdiagnosis is not unique to melanoma screening but is prevalent in screening for cancers of other organs, including the thyroid and prostate glands.

Risk of breast cancer among Japanese women with a positive family history.

191 Background: Most breast cancer cases are sporadic, rather than associated with inherited gene mutations, such as BRCA1 and BRCA2. However, women with a family history of breast cancer are at increased risk of developing breast cancer compared to those women without any family history, even if they lack these gene mutations. Methods: We analyzed 10892 patients including bilateral breast cancer cases (total of 11398 breast cancers) who underwent surgery at our hospital between 1962 and 2009. We excluded 295 cases whose family history data were not available. Clinical and pathological differences between following patient groups were tested; 9528 patients or 9955 cancers (88%) with negative family history (FH-), 896 patients or 951 cancers (8%) who had at least one first-degree relative with breast cancer (1FH+), 468 patients or 492 cancers (4%) who had second-degree relative with breast cancer (2FH+), and 1364 patients or 1443 cancers (12%) with family history regardless of first- or second-degree relative (FH+). Significance was established at a p-value of &lt; 0.05. Results: Among the family members, sisters were more likely to have treated for breast cancer (38% in FH+ group), followed by mothers (27%), aunts (26%), grandmothers (7%), and daughters (2%). The incidence of developing contralateral breast cancer was significantly higher in 1FH+ group, compared to patients in FH- and 2FH+ groups. No other factors showed any significant difference, including the incidence of cancer in other organs, pathological characteristics, and age of onset, although BRCA1 and BRCA2 mutation may be associated with increased risk of developing breast cancer at younger age. Outcome studies with available data did not show any significant difference in overall survival between FH+ and FH- patients. Conclusions: A Japanese woman with a positive family history has a higher risk of developing breast cancer than women without any close relatives with breast cancer, similar to the results reported in Western countries where prevalence of breast cancer is higher. Regular checkup of contralateral breast is important for those patients whose first-degree relatives have also been diagnosed with breast cancer.

Abstract 1326: Systems approach to identifying potential environmental exposures playing a role in ovarian carcinogenesis

Abstract Other than an association of a small fraction with inherited mutations in BRCA1 and BRCA2, most cases of ovarian cancer (OvCa) are sporadic with cause unknown. Identifying environmental exposures that may contribute to ovarian carcinogenesis would provide the basis for epidemiological studies to determine other causes of OvCa. Environmental exposures are capable of inducing epigenetic changes that result in changes in gene expression. Most importantly, changes in microRNA expression may cause permanent changes in regulation of gene expression patterns leading to altered cellular phenotypes. These alterations in microRNAs represent dysregulation in the cancer cells and may be a manifestation of environmental exposures. Thus, we hypothesized that circulating microRNAs associated with OvCa are biomarkers of exposure and could be used to identify gene expression changes resulting from environmental exposures. We employed a systems approach utilizing publicly available data for elevated levels of circulating microRNAs associated with OvCa and for altered gene expression in ovarian cancers in conjunction with associations between chemical exposures and gene expression compiled in the Comparative Toxicogenomics Database (CTD) to identify chemicals that may play a role in ovarian carcinogenesis. Intersection of genes with altered expression in ovarian cancer and putative gene targets of microRNAs identified in plasmas of OvCa patients gave a list of candidate genes for chemical interactions. Ingenuity Pathway analyses of these genes show that they participate in pathways involved in cancer and other chronic diseases. This list of genes was submitted to the CTD and a list of chemicals with known interactions with these genes was collected. The list of chemicals interacting with the OvCa specific genes included known carcinogens (arsenic, asbestos, benzo[a]pyrene), co-carcinogens (tetrachlorodibenzodioxin, tetradecanoylphorbol acetate), peroxides, heavy metals (Cu, Zn), epigenotoxicants (hydralizine, valproic acid), inflammation inducers (zymosan, lipopolysaccharide), steroid hormones (estradiol, progesterone, dexamethasone), dietary chemopreventives (indole-3-carbinol, curcumin) and chemotherapeutics (doxorubicin, tamoxifen). While some of these chemicals and pathways have been implicated previously in ovarian carcinogenesis, many have not and their identification will enable the development of targeted epidemiological studies to determine the role of their exposure in inducing or preventing OvCa. This systems approach may be useful to identify environmental exposures contributing to cancer of other organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1326. doi:10.1158/1538-7445.AM2011-1326

Long-term patient outcome 10 years after video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer

Introduction: Although there have been many reports associating video-assisted thoracoscopic surgery (VATS) with improved survival rates in early lung cancer, almost all of the reports have involved short median follow-ups and been presented at a 5-year point. Here, we establish the pattern and frequency of recurrences, as well as the long-term survival rates of patients who have undergone VATS more than 10 years ago. Methods: We retrospectively studied 41 patients who underwent VATS lobectomy for clinical stage I non-small-cell lung cancer at Fukuoka University Hospital between November 1994 and December 1999. All patients underwent lobectomy, including a dissection of hilar and mediastinal lymph nodes. Follow-up consisted of clinical and radiological examinations every 3 months for the first 2 years after the surgery and then once a year thereafter. Results: Of the 41 patients, 31 were diagnosed to be at pathologic stage IA and six at stage IB, while the remaining four were more advanced cases. During the follow-up period, recurrences were found in five cases (12.2%). Four patients with recurrence died of lung cancer and an additional two died from cancers of other organs. There were other non-cancer related deaths, largely from respiratory failures. Overall, the 5- and 10-year survival rates after the operation were 79.8% and 68.8%, respectively. Conclusion: Long-term survival and recurrence rates after a classic VATS lobectomy for lung cancer are favorable compared to the conventional approach.

Clinical course and outcome after esophagectomy with three-field lymphadenectomy in esophageal cancer

Esophagectomy with three-field lymphadenectomy has been performed for esophageal cancer. Detailed analysis of cause of death and mode of recurrence is required to determine the need for further adjuvant therapy and follow-up. A total of 208 patients who underwent esophagectomy through right thoracotomy with three-field lymphadenectomy were enrolled into the present study. Mode of first recurrence was divided into four groups: lymph node, hematogenous, mixed, and local recurrence. Excluding 16 hospital deaths, the number of deaths and 5-year survival rates were 104 patients and 7.8% for cancer recurrence, 12 patients and 53.8% for second primary cancers in other organs, and 34 patients and 31.0% for causes of death unrelated to carcinoma. In the 104 patients with relapse, 5-year survival rate of patients was 14.3% with lymph node recurrence (n = 29), 9.1% with hematogenous recurrence (n = 32), 3.1% with mixed recurrence (n = 35), and 12.5% with local recurrence (n = 8). To improve outcomes for esophagectomy with three-field lymphadenectomy, early detection of recurrent disease and regular examination of the entire body for secondary cancer is necessary.

Germ-Line Mutations, Pancreatic Inflammation, and Pancreatic Cancer

The fundamental problem underlying pancreatic cancer is altered genetics. Rare germ-line mutations lead to familial cancer syndromes that may include pancreatic cancer. But why do some people develop pancreatic cancer while others develop cancer in other organs, or not at all? We discuss the possibility that other common germ-line mutations diminish the ability of pancreatic cells to protect themselves from environmental or metabolic stressors, resulting in reactive molecules that lead to cell injury and DNA damage-with a series of lucky hits knocking out key tumor-suppressor genes and activating oncogenes in at least one cell with clonal growth potential. Inflammation likely accelerates this process, whether or not it is clinically evident. We also note the significant effects of smoking, alcohol, antioxidants, and diet on risk, and that together they confer a major portion of attributable risk that may be linked to the injury-inflammation-cancer pathway. Because we cannot change our genes, lifestyle choices are currently the best way to reduce pancreatic cancer risk until more effective preventative strategies are developed.

Role of KCNMA1gene in breast cancer invasion and metastasis to brain

BackgroundThe prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion.MethodsWe performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX).ResultsThe Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1.ConclusionDetermining the relative abundance of BKCa channel expression in breast cancer metastatic to brain and the mechanism of its action in brain metastasis will provide a unique opportunity to identify and differentiate between low grade breast tumors that are at high risk for metastasis from those at low risk for metastasis. This distinction would in turn allow for the appropriate and efficient application of effective treatments while sparing patients with low risk for metastasis from the toxic side effects of chemotherapy.

An epidemiological study to identify the risk factors with two different types of controls in high-grade cervical lesions including invasive cancer

A multidisciplinary study on pre-cancerous and early cancerous lesions of uterine cervix was carried out at our Institute from which the subjects (cases and one group of control) for the present study were selected with the objective to identify the possible risk factors related to high-grade cervical lesions including invasive cancer through an epidemiological study by selecting two different types of controls and to assess the feasibility whether the cancers of other organs could be taken as controls at the same time studying the risk factors associated with cervical cancer. One group of control was women with negative Pap smear and second group of control was the women with breast cancer but negative Pap smear. A total of 100 biopsy-proven cases of high-grade cervical intraepithelial lesions and Invasive cancer were recruited. The results of the study show that some of the risk factors associated with the cervical cancer get exaggerated when breast cancer cases were used as controls because risk factors of both cancers are opposite to each other. So it is concluded that in order to remove any bias, normal hospital controls or controls selected from multiple cancers should be taken to study the risk factors involved in cervical carcinogenesis.

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain.

Abstract Abstract #2043 Background: The prognosis for patients with brain metastasis from breast cancer is extremely poor. A significant number of breast tumor patients despite aggressive therapy develop metastatic disease in brain. The mechanism or the cause of breast cancer metastasis to brain is unknown. Therefore, it is critical to identify prognostic molecular markers of the metastatic process in order to design therapeutic modalities for reducing the occurrence of metastasis. In this study we investigated KCNMA1 gene, which encodes alpha subunit of calcium activated potassium (KCa) channels. Altered KCa channels, are described in a wide variety of tumor cell types and up-regulation of KCa channels was shown to be a novel mechanism for the malignant phenotype of human tumor cells.&amp;#x2028; Material and Methods: We performed Global GeneChip exon arrays to study the expression of KCNMA1 gene in metastatic breast cancer in brain and compared it with primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immuno-histochemistry was performed to study the expression and localization of alpha subunit of KCa channel protein in primary and metastatic breast tumor tissues and breast cancer cell lines. We performed Matrigel invasion, transendothelial migration and membrane potential assays in normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether KCa channel inhibition attenuates breast tumor invasion and metastasis to brain.&amp;#x2028; Results: The Global GeneChip exon array and RT-PCR showed higher KCNMA1 gene expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased KCa channel activity, leading to greater invasion and trans-endothelial migration, which could be attenuated by blocking the KCNMA1 gene with siRNA and biochemical inhibition with IBTX.&amp;#x2028; Discussion: Recent investigations in patients with metastatic lung and breast cancers reported alarming rates of brain metastases. Unraveling the genetic aberrations that drive the metastatic events in these cancer cells offer insights into how to limit or prevent this lethal process. For instance, determining the relative abundance of KCNMA1 gene in breast cancer metastasis to brain and understanding the mechanism of brain metastasis provides a unique opportunity to identify specific genetic markers that could differentiate between low grade breast tumors that are at high risk for metastasis from those at low risk for metastasis. This would in turn allow for the appropriate and efficient application of treatments to obtain the greatest benefit while sparing low risk patients for metastasis from the toxic side effects of chemotherapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2043.

Bile acids as endogenous etiologic agents in gastrointestinal cancer

Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.

Defect of Hepatocyte Growth Factor Activator Inhibitor Type 1/Serine Protease Inhibitor, Kunitz Type 1 (Hai-1/Spint1) Leads to Ichthyosis-Like Condition and Abnormal Hair Development in Mice

Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase inhibitor initially identified as an inhibitor of hepatocyte growth factor activator. It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and function. In this study, skin and hair phenotypes of mice lacking the Hai-1/Spint1 gene were characterized. Previously, we reported that the homozygous deletion of Hai-1/Spint1 in mice resulted in embryonic lethality attributable to impaired placental development. To test the role of Hai-1/Spint1 in mice, the placental function of Hai-1/Spint1-mutant mice was rescued. Injection of Hai-1/Spint1(+/+) blastocysts with Hai-1/Spint1(-/-) embryonic stem cells successfully generated high-chimeric Hai-1/Spint1(-/-) embryos (B6Hai-1(-/-High)) with normal placentas. These embryos were delivered without apparent developmental abnormalities, confirming that embryonic lethality of Hai-1/Spint1(-/-) mice was caused by placental dysfunction. However, newborn B6Hai-1(-/-High) mice showed growth retardation and died by 16 days. These mice developed scaly skin because of hyperkeratinization, reminiscent of ichthyosis, and abnormal hair shafts that showed loss of regular cuticular septation. The interfollicular epidermis showed acanthosis with enhanced Akt phosphorylation. Immunoblot analysis revealed altered proteolytic processing of profilaggrin in Hai-1/Spint1-deleted skin with impaired generation of filaggrin monomers. These findings indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of the epidermis and hair development.

Síndrome de Lynch: Caracterización genético clínica. Caso clínico

Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene.

Investigation of micronucleus frequencies in lymphocytes of inhabitants environmentally exposed to chrysotile asbestos

Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. Many of the regions of Turkey have asbestos deposits. People in Doğanlı village – one of these regions – have been environmentally exposed to chrysotile asbestos since they were born. In this study the effects of asbestos on micronucleus (MN) frequencies of inhabitants exposed to chrysotile asbestos have been examined. Thirty subjects who had been environmentally exposed to chrysotile asbestos and living in Doğanlı village, and 25 controls were studied to assess the MN frequency. The control group was selected from healthy individuals with no exposure to asbestos and living in similar geographic conditions to Doğanlı village. Peripheral blood samples were collected from each subject and cultured for MN assay. Cytochalasin-B was added to lymphocyte cultures for evaluation of MN in binucleated (BN) cells. The differences between those exposed to chrysotile asbestos and controls were not statistically significant in terms of BN cells with MN (p > 0.05). There was not a significant relationship between MN frequencies and age, sex, smoking, both in chrysotile asbestos-exposed subjects and in controls (p > 0.05). Although the detection of calcified pleural plaques found in the inhabitants has indicated environmental exposure to chrysotile asbestos, our results show that chrysotile asbestos was not an inducer of MN in subjects exposed to chrysotile asbestos.

Recurrent Breast Cancer Presents as a Single Solid Ovarian Mass and Ascites

Ovarian malignancy is highly suspected when patients present with an ovarian cystic mass lesion accompanied with ascites. However, aside from the primary origin, a metastatic lesion should be considered, since the ovary is frequently metastasized from cancers of other organs, such as the genital tract, gastrointestinal tract, and breast. Herein, we report the case of a patient with a left adnexal mass and ascites to emphasize consideration of metastatic ovarian tumors from non-gynecologic organs. A 47-year-old woman with a history of right breast infiltrating lobular carcinoma, T3N0M0, grade 3, was treated with modified radical mastectomy and axillary lymph-node dissection in July 2001. Tumor recurrence was noted in December 2003. Therefore, she underwent palliative radiotherapy and various kinds of chemotherapy. In March 2006, she experienced poor appetite and abdominal fullness, and was found to have a 12-cm adnexal mass accompanied with ascites. Ovarian cancer was suspected, and exploratory laparotomy was performed. However, metastatic carcinoma of the ovary of breast origin was finally diagnosed. In cases of pelvic tumors in patients who have a history of other primary cancers, metastasis should be suspected initially. Although the prognoses of these patients seem to be worse, intensive cytoreductive surgery would improve quality of life and offer a chance of better survival in highly selected patients.

Clinical Characteristics of Patients with Sporadic Colorectal Cancer and Primary Cancers of Other Organs

Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%), either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years). The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2%) and six breast cancers (35.2%) were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer patients with hematochezia or gastrointestinal symptoms/signs should be evaluated for the possibility of second primary CRC during their regular follow-up.

Erbliches Endometrium- und Ovarialkarzinom bei Patientinnen mit Lynch-Syndrom

Das Endometrium- wie auch das Ovarialkarzinom können Bestandteil eines Lynch-Syndroms/HNPCC sein. Für Patientinnen mit Lynch-Syndrom/HNPCC besteht zusätzlich ein Tumorrisiko im Bereich des Dickdarms und in anderen Organsystemen. Deshalb benötigen diese Patientinnen sowie deren Familienangehörige ein komplexes Früherkennungsprogramm, das ein interdisziplinäres Betreuungskonzept zur Voraussetzung hat. Die klinischen Aspekte sowie Grundzüge der Genetik des Lynch-Syndroms/HNPCC werden erläutert, Untersuchungen zur Tumorfrüherkennung sowie die genetische Beratung und Diagnostik werden vorgestellt.

Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer

Purpose: The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center.Patients and methods: We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3–16.3 years) from 1739 women aged 30–70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral).Results: The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67–1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46–0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63–2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival.Conclusions: Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.