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Wednesday, October 07, 2015

Identification of germline genetic mutations in patients with pancreatic cancer



Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC.


A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified. Clinical data, family history, and germline results were evaluated.


Among 159 patients with PAC who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval, 9.5%-20.7%), including BRCA2 (13 mutations), BRCA1 (4 mutations), p16 (2 mutations), PALB2 (1 mutation), and Lynch syndrome (4 mutations). BRCA1/BRCA2 prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in non-AJ patients (56 patients). In AJ patients with a strong, weak, or absent family history of BRCA-associated cancers, the mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all mutation carriers was 58.5 years (range, 45-75 years) compared with 64 years (range, 27-87 years) in those not carrying a mutation (P = .02). Although BRCA2 was the most common mutation identified, no patients with early-onset PAC (diagnosed at age ≤ 50 years) harbored a BRCA2 mutation and the mean age at diagnosis in BRCA2 carriers was equivalent to that of individuals who were not mutation carriers (P = .34). Mutation prevalence in patients with early-onset disease (21 patients) was 28.6%, including BRCA1 (2 mutations), p16 (2 mutations), MSH2 (1 mutation), and MLH1 (1 mutation).

Mutations in BRCA2 account for > 50% of patients with PAC with an identified susceptibility syndrome. AJ patients were found to have high BRCA1/BRCA2 prevalence regardless of personal/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of BRCA2-associated PAC, an inherited predisposition for PAC is associated with an earlier age at PAC diagnosis, suggesting that this subset of patients may also represent a population warranting further evaluation.

Tuesday, October 06, 2015

Biological Therapies for Cancer - National Cancer Institute


Pathology of cancers of the female genital tract

open access

The future role of molecular staging in gynecologic cancer

open access

 Article outline

Cancer of the ovary, fallopian tube, and peritoneum - FIGO Cancer Report 2015

open access
In 2014, the Gynecologic Oncology Committee of FIGO revised the staging to incorporate ovarian, fallopian tube, and peritoneal cancer in the same system. Changing the staging system required extensive international consultation. The primary site (i.e. ovary, fallopian tube, or peritoneum) is designated, where possible. When it is not possible to clearly delineate the primary site, these should be listed as “undesignated” [1] and [2].
It has been presumed that fallopian tube malignancies were rare [2].....
 Article outline

Psychosexual health in gynecological cancer

open access

4.2. Ovarian cancer

It has been known for some time that the physical and emotional impact of ovarian cancer can be devastating, leading to sexual as well as global quality of life issues [20]. One study has shown a prevalence of 63% for sexual difficulties among women with a diagnosis of ovarian cancer [3]. The effects of chemotherapy and surgery, combined with the anxiety about survival can have a dramatic negative effect on the woman’s libido, and even women who undertake risk-reducing salpingo-oophorectomy can suffer sexual dysfunction [21]. Many of these women are totally unprepared for the devastating effects of sudden menopause, with hot flushes, vaginal dryness, and loss of libido replacing a previously healthy sex life. This could be helped by more realistic counselling before the procedure, and increased postoperative emotional support.

To Treat or Not to Treat: The Use of Hormone Replacement Therapy in Patients With Ovarian Cancer

Editorial: open access

.... Eeles et al16 are to be congratulated for recognizing the importance of this study and observing the accrued cohort for nearly two decades. These findings, unlikely to be repeated, support the hypothesis that HRT improves outcomes in patients with ovarian cancer by reducing ovarian cancer relapse, ovarian cancer-specific death, and other causes of death. In the Women's Health Initiative study, estrogen did not significantly affect all-cause mortality, making the decrease in mortality in the patients studied here of interest.10
Where do we stand in 2015? To treat or not to treat? Although there are many unanswered questions (eg, the mechanisms of how estrogen improves OS, the optimal duration of therapy), the data from Eeles et al16 combined with that of previous studies allow oncologists to feel comfortable offering patients HRT after the treatment of EOC to reduce vasomotor and other postmenopausal symptoms and should, therefore, improve the quality of life for patients with epithelial ovarian cancer
  See accompanying article doi:10.1200/JCO.2015.60.9719


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Monday, October 05, 2015

Early epithelial lesions in prophylactic annexectomies in patients at high risk of ovarian cancer

 [Early epithelial lesions in prophylactic annexectomies in patients at high risk of ovarian cancer: Report of a series of 93 cases]


Tubal lesions detected in specimen of risk reducing salpingo oophorectomy (RRSO) for mutation BRCA1/2 seems to play a role in ovarian carcinogenesis. The main objective of this study is to evaluate the prevalence of occult neoplasia, of Serous Tubal Intraepithelial Carcinoma (STIC), and signature P53 in a cohort of patients who underwent a risk reducing salpingo oophorectomy.


From January 2010 to January 2014 unicentric, retrospective study on a consecutive cases cohort of RRSO for patients with a high risk of ovarian neoplasia (mutation BRCA 1/2 or family history). Pathological specimen should be analysed according to the SEE-FIM protocol.


Ninety-three RRSO were recorded. Among them, 44% of the patients had the germ line mutation BRCA1, 30.1% BRAC2 and 18.2% had no identified mutation. In all, 33.3% of the RRSO reveal a signature P53, in the fimbria for 93.9%, 7.9% of them were bilateral. 1,1‰ (n=1) of the patients presented a unilateral STIC. We obtained 4.3% of occult neoplasia: 3 ovarian high-grade serous carcinomas and 1 tubal high-grade serous carcinoma. Only the tubal carcinoma coexists with STIC.


5,4% of the patients who underwent RRSO had a diagnostic of occult neoplasia. One percent of the patients had an isolated STIC. These results agree with recent data of the literature. Extensive examination of the Fallopian tube opens up a new way to understand ovarian carcinogenesis.

Editorial: Genetic Testing for BRCA Mutations Today and Tomorrow—About the ABOUT Study

JAMA Network

Women tested for breast-cancer mutations often miss out on key counselling

CBC News

Sunday, October 04, 2015

The wisdom of patients and families: ignore it at our peril

open access

Experts critical of America's right-to-try drug laws - The Lancet

Experts critical 

Rise in online pharmacies sees counterfeit drugs go global - The Lancet

counterfeit drugs go global 

Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count/baseline clinical parameters

Risk factors (abstract)


Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma. Its original formulation is metabolized by the monocyte-macrophage system. One of its main toxicities is the palmoplantar erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have been identified.


Data of patients (pts) treated with PLD between 2005 and 2014 were retrospectively collected. A case-control study was performed, comparing main baseline clinical and biological characteristics of pts experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocyte subpopulations (classical, intermediate and non-classical) was performed by FACS in selected pts.


Among 88 pts treated with PLD, 28 experienced PPE of any grade (31, 95 % CI 21-41). The first occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32 %) and represented 57 % of cases after cycle 3. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. Older pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi-square test). Monocyte count and inflammatory parameters were not associated with PPE. However, the analysis of monocyte subpopulations revealed a large inter-patient variability.


Contrary to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte subpopulations may have different roles on PLD metabolism and warrant further studies.

Annual report of the Committee on Gyn Oncology, the Japan Society of Obstetrics and Gynecology


 Article first published online: 30 SEP 2015

The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. Here we present the Treatment Annual Report for 2007. Data on the prognosis of 3381 patients with cervical cancer, 3681 with endometrial cancer, and 2367 with ovarian cancer for whom treatment was initiated in 2007 were analyzed in the Treatment Annual Report. In the 2007 Treatment Annual Report, stage I accounted for 53.1%, stage II for 24.4%, stage III for 14.2%, and stage IV for 8.3% of all patients with cervical cancer. Stage I accounted for 64.8%, stage II for 8.2%, stage III for 20.2%, and stage IV for 6.9% of all patients with endometrial cancer. Stage I accounted for 41.4%, stage II for 9.9%, stage III for 30.6%, and stage IV for 8.6% of all patients with ovarian cancer.
The 5-year overall survival rates for patients with cervical cancer were 91.8% for stage I, 71.5% for stage II, 53.0% for stage III, and 23.7% for stage IV; those for patients with endometrial cancer were 95.3%, 89.8%, 75.6%, and 29.1%, and those for patients with ovarian surface epithelial–stromal tumors were 91.5%, 76.1%, 46.9%, and 31.3%, respectively.

Editorial: Is UK cancer care broken? - The Lancet Oncology

The Lancet Oncology

New Ontario Cancer Registry rules increase t...

New Ontario Cancer Registry rules 
 September 2015

In October 2014, the Ontario Cancer Registry (OCR) implemented a new set of rules for identifying multiple primary cancers, which has led to an increase in the number of reported cases for certain cancer types. The OCR is the provincial database containing information about all newly diagnosed cancer cases in Ontario, except for basal cell and squamous cell carcinomas of the skin, and its new rules are applied to cases diagnosed from 2010 onwards.
Multiple primary cancers are two or more distinct cancers that occur in one person and are different from metastases, which develop when cells from a primary cancer spread to other parts of the body. The new rules, which follow standards for counting multiple primary cancers defined by the National Cancer Institute’s Surveillance, Epidemiology and End Results (NCI SEER) Program, replaced rules that were a modified version of the International Association of Cancer Registries (IACR) standards. With the new rules, the number of newly diagnosed cancer cases registered by the OCR in 2010–2011 is 5.8 per cent higher than the number of cases that would have been reported using the old rules.....

$16M funding for research into high-risk, inherited cancers ($$ Terry Fox Foundation...)

$16M funding

 This year is the 35th anniversary year of the Terry Fox Marathon of Hope, and the Terry Fox New Frontiers Program Project Grant program was created over 30 years ago. A highly competitive program, funds are awarded annually to support breakthrough and transformative biomedical research which may form the basis for innovative cancer prevention, diagnosis and/or treatment. Launched in October 2007, the Terry Fox Research Institute is the brainchild of The Terry Fox Foundation and today functions as its research arm.

Editorial: Genetic Testing for BRCA Mutations Today and Tomorrow—About the ABOUT Study

JAMA Network Article

Armstrong  J, Toscano  M, Kotchko  N,  et al.  Utilization and outcomes of BRCA genetic testing and counseling in a national commercially insured population: the ABOUT study [published online October 1, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.3048.
Metcalfe  K, Lynch  HT, Foulkes  WD,  et al.  Effect of oophorectomy on survival after breast cancer in BRCA1 and BRCA2 mutation carriers. JAMA Oncol. 2015;1(3):306-313.
PubMed   |  Link to Article
Metcalfe  K, Gershman  S, Ghadirian  P,  et al.  Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ. 2014;348:g226.
PubMed   |  Link to Article
Finch  AP, Lubinski  J, Møller  P,  et al.  Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014;32(15):1547-1553.
PubMed   |  Link to Article
Metcalfe  KA, Mian  N, Enmore  M,  et al.  Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening. Breast Cancer Res Treat. 2012;133(2):735-740.
PubMed   |  Link to Article
Gronwald  J, Huzarski  T, Byrski  T,  et al.  Direct-to-patient BRCA1 testing: the Twoj Styl experience. Breast Cancer Res Treat. 2006;100(3):239-245.
PubMed   |  Link to Article
Metcalfe  KA, Poll  A, Royer  R,  et al.  A comparison of the detection of BRCA mutation carriers through the provision of Jewish population-based genetic testing compared with clinic-based genetic testing. Br J Cancer. 2013;109(3):777-779.
PubMed   |  Link to Article

GPs being paid to cut patient referrals - BBC News

BBC News

Characteristics of ovarian tumors of low malignant potential in BRCA mutation carriers: A case series

open access

 Article Outline


  • Tumor characteristics of 5 cases of ovarian tumor of low malignant potential (LMP) with BRCA mutation were examined.
  • Young age, BRCA1 mutation, and presence of invasive implants may be characteristics of BRCA carriers with ovarian LMP.

Ovarian Germ Cell Tumors Treatment (PDQ®)

PDQ Cancer Information Summaries - NCBI Bookshelf

Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention (PDQ®)

 PDQ Cancer Information Summaries - NCBI Bookshelf

The Risk of Epithelial Ovarian Cancer of Women With Endometriosis May be Varied Greatly if Diagnostic Criteria Are Different

open access

 The Risk of Epithelial Ovarian Cancer of Women With Endometriosis May be Varied Greatly if Diagnostic Criteria Are Different: A Nationwide Population-Based Cohort Study

 .....The risk of EOC in women with endometriosis varied greatly by different criteria used. Women with endometriosis might have a more apparently higher risk than those reported by systematic review and meta-analysis.


Dr. Sampson in 1925 proposed a possible correlation between endometriosis and malignant transformation (occurrence of epithelial ovarian cancer [EOC]); thereafter, many epidemiologic studies, including recent systematic reviews1–9 and meta-analyses,3,4,10–12 indicated that women with endometriosis might have an increased risk of EOC. Although epidemiologic studies have not always supported a positive correlation between endometriosis and EOC,13–15 other studies have reported an unusually high risk of EOC in women with diagnosed endometriosis.16,17 The question is, why has the risk of EOC in women with endometriosis varied in different studies, ranging from no correlation in Olson study....

A Systematic Review of Nonpharmacologic Interventions for Treatment-Related Symptoms in Women With Ovarian Cancer

open access (full text - click pdf)

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial


Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis


 Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized.

We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs 11 months), 1 year OS: 35% vs 47% (p=0.05), 2 year OS: 16% vs 31% (p<0.01), and 5 year OS: 7% vs 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.

A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors (Sertoli-Leydig cell tumors)


Dose-finding quantitative FDG PET imaging study with the oral pan-AKT inhibitor GSK2141795 in patients with gyn malignancies


Interleukin-12 Immunomodulation Delays the Onset of Lethal Peritoneal Disease of Ovarian Cancer


 The omental fat band (OFB) is the predominant site for metastatic seeding of ovarian cancer. Previously, we highlighted the influx and accumulation of neutrophils and macrophages in the OFB following syngeneic ovarian cancer cell seeding as an important factor in the development of a protumorigenic cascade. Here we investigated localized immunomodulation as a means of promoting a successful protective response. As an important TH1-type immunomodulator, interleukin (IL)-12 has previously been investigated clinically as an anticancer therapeutic. However, systemic IL-12 administration was associated with serious side effects, galvanizing the development of immune or accessory cells engineered to express secreted or membrane-bound IL-12 (mbIL-12). Using an mbIL-12-expressing cell variant, we demonstrate that localized IL-12 in the tumor microenvironment significantly delays disease development. The mbIL-12-mediated decrease in tumor burden was associated with a significant reduction in neutrophil and macrophage infiltration in the OFB, and correlated with a reduced expression of neutrophil and macrophage chemoattractants (CXCL1, -2, -3 and CCL2, -7). Vaccination with mitotically impaired tumor cells did not confer protection against subsequent tumor challenge, indicating that IL-12 did not impact the immunogenicity of the cancer cells. Our findings are in agreement with previous reports suggesting that IL-12 may hold promise when delivered in a targeted and sustained manner to the omental microenvironment. Furthermore, resident cells within the omental microenvironment may provide a reservoir that can be activated and mobilized to prevent metastatic seeding within the peritoneum and, therefore, may be targets for chemotherapeutics.

Migraine during perimenopause (HRT/surgical menopause)

invited speaker presentation

..... Natural menopause is associated with a lower incidence of migraine as compared with surgical menopause[8]; data on migraine prevalence in relation to the type of surgical procedure are till now unclear and contradictory[9].

Implementing a home-based exercise program for patients with advanced, incurable diseases after discharge and their caregivers: lessons we have learned

Full text 



The acceptability for participation on the part of the patients can be considered as low because only one patient out of 11 eligible patients gave informed consent (Fig. 1). However, the decision for not participating is multifactorial and could probably not be summarized in a single reason. It is hardly possible to judge whether the given reason, the complex overall situation, the study design, the intervention, other reasons or a combination of these factors have led to the patients’ decision. The low number of eligible patients can be traced back to our eligibility criteria, which apparently was not appropriate, and the low acceptability may be a consequence of different recruitment barriers (see paragraphs below).
No patient completed the study. Therefore, no judgement can be made on the efficacy of the intervention for this population (expansion) [16]......

Whole-body diffusion-weighted MRI for staging of women with cancer during pregnancy: a pilot study

poster presentation

Tumour characterisation, staging and operability assessment in ovarian carcinoma: whole body diffusion-weighted MRI versus CT

poster presentation

Fertility preservation in gynaecologic malignancy: imaging role in treatment planning

poster presentation

Ovarian cancer: imaging in treatment selection and planning with FIGO update

Oral presentation

.... FIGO has recently revised the staging of ovarian cancer [1]. It includes a revision of the stage III patients and allotment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dis-semination, because an analysis of these patients indicates that their survival is significantly better than those who have intraperitoneal dissemination [1]...

Benign lesions that mimic cancer: Ovarian

oral presentation

Detection of gynaecological cancer in pregnancy

poster presentation

Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations - Urology


To evaluate the risk of urothelial cancer in the upper urinary tract and the bladder, determine the contribution from the different mismatch-repair genes and define clinical characteristics of urothelial cancer in Lynch syndrome.


The national hereditary nonpolyposis colorectal cancer registry was used to identify all 288 Lynch syndrome families in Denmark. Urothelial cancers that developed in mutation carriers and in their first-degree relatives were identified, mismatch-repair status was assessed, clinico-pathologic variables were defined and cumulative life-time risks were determined.


In total, 48 cancers of the ureter, 34 cancers of the renal pelvis and 54 urinary bladder cancers developed at a mean age of 61 (24-89) years. The tumors were typically of high grade, showed loss of mismatch repair protein expression in 90% of the tumors and microsatellite instability in 23% of the tumors. Mutations in MSH2 were overrepresented (73%) and MSH2 mutation carriers were at significantly increased risk of urinary tract cancer compared individuals with mutations in MLH1/MSH6.


Cancers of the upper urinary tract as well as the urinary bladder are included in the Lynch syndrome tumor spectrum. Urothelial cancers are predominantly linked to MSH2 mutations, which suggest that surveillance should be targeted at individuals with mutations herein.