NCCN 2015 Genetic/Familial High-Risk Assessment: Colorectal

NCCN (references to non-polyposis/polyposis syndromes/Li-Fraumeni... + changes re: breast cancer also note: urothelial)

MSH1/2 + EPCAM mutation carriers

 There are data to suggest that aspirin may decrease the risk of colon cancer in LS; however, at this time the data are not sufficiently robust to make a recommendation for its standard use.

Extracolonic:

Endometrial and ovarian cancer:

Prophylactic hysterectomy and bilateral salpingo-oophorectomy (BSO) is a risk-reducing option that should be considered by women who have completed childbearing.

Patients must be aware that dysfunctional uterine bleeding warrants evaluation.

There is no clear evidence to support screening for endometrial cancer for LS. However, annual office endometrial sampling is an option.

While there may be circumstances where clinicians find screening helpful, data do not support routine ovarian screening for LS. Transvaginal ultrasound for ovarian and endometrial cancer has not been shown to be sufficiently sensitive or specific as to support a positive recommendation, but may be considered at the clinician’s discretion. Serum CA-125 is an additional ovarian screening test with caveats similar to transvaginal ultrasound.

Gastric and small bowel cancer: 

There is no clear evidence to support screening for gastric, duodenal, and small

bowel cancer for LS. Selected individuals or families or those of Asian descent

may consider EGD with extended duodenoscopy (to distal duodenum or into the jejunum) every 3–5 y beginning at age 30–35 y.

Urothelial

Consider annual urinalysis starting at 25–30 y.

 Central nervous system (CNS) cancer: 

Annual physical/neurologic examination starting at 25–30 y; no additional screening recommendations have been made.

Pancreatic cancer:  

Despite data indicating an increased risk for pancreatic cancer, no effective screening techniques have been identified; therefore, no screening recommendation is possible at this time.

Breast cancer: There have been suggestions that there is an increased risk for breast cancer in LS patients; however, there is not enough evidence to support increased screening above average-risk breast cancer screening recommendation

NCCN Guidelines Version 2.2015 Genetic/Familial High-Risk Assessment: Breast and Ovarian

NCCN Guidelines (93 pages also includes references to Cowden Syndrome/Lynch Syndrome/Li-Fraumeni....)

Oxaliplatin for the treatment of ovarian cancer, Expert Opinion on Investigational Drugs

abstract
 

Introduction: Oxaliplatin is an important drug in treatment of several solid tumors. Ovarian cancer (OC) is sensitive to chemotherapy and the overall response rate with primary therapy is about 75%. Unfortunately, 60 – 70% of patients experience recurrence requiring additional treatments and finally die of progressive disease within 5 years of the initial diagnosis. Currently, a platinum-based combination therapy is recommended in platinum-sensitive disease while a non-platinum single-agent therapy is preferred in platinum-resistant disease that is characterized by a low response rate.

Areas covered: In this article, the authors review the Phase II and Phase III studies of oxaliplatin as an OC therapy. Furthermore, the authors discuss the pharmacokinetic and pharmacodynamic features of oxaliplatin.

PARP inhibitors in the management of breast cancer: current data and future prospects

open access
 

Abstract

Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics.

Pain typology and incident endometriosis

abstract
 

WIDER IMPLICATIONS OF THE FINDINGS:

Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed.

Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread

abstract

 Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread: A Retrospective Cohort Study

 OBJECTIVE: 

This study aimed to determine surgical outcomes related to hand-assisted robotic surgery (HARS) for staging of ovarian cancer and uterine cancers with high risk of peritoneal spread and compare them to laparotomy and standard robotic-assisted surgery.

Usefulness of Multigene Testing: Catching the Train That’s Left the Station

Commentary - open access (breast/ovarian genes)

Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis

abstract (UK)

 BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2–3 % per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy

open access


 Abstract
Women with an increased lifetime risk of ovarian cancer are advised to undergo risk-reducing salp-ingo-oophorectomy (RRSO) to reduce risk of adnexal
cancer. We investigated the uptake of RRSO and evaluatedthe influence of personal medical history of (breast) cancer,risk-reducing mastectomy (RRM) and family history of ovarian and/or breast cancer on the RRSO decision......
 
 Study population
The study population consists of all women who received
counseling for RRSO, based on the criteria described pre-
viously. Women who had completed childbearing at
<35 years of age and had received counseling for RRSO
were included too.
Women previously diagnosed with ovarian cancer, car-
riers of a mutation in one of the MMR genes (predisposing
to Lynch syndrome), women with increased risk of breast
cancer or other non-breast and ovarian related hereditary
tumors only, were excluded.......

 


















 In conclusion, the majority (87.2 %) of the women carrying a BRCA mutation or having familial susceptibility to ovarian cancer, who visited our clinic, where it

is not offered, opted for RRSO. This decision is made relatively quick; the majority decided after the first consultation with the gynecologist. This approach is therefore likely to be effective in reducing ovarian cancer related mortality in this high risk population. Personal medical history of (breast) cancer was not found to significantly affect the decision to undergo RRSO, though women who had undergone RRM were more likely to opt for RRSO. Also, patients with 1st degree relatives who had breast cancer needed significantly less consultations to decide for RRSO