Author: Lynch Syndrome Ireland

Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice

Background

The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.

Conclusions

Whilst consensus recommendations were achieved, the meeting highlighted some of the barriers limiting the use of CanRisk in clinical practice and identified areas that require further work and collaboration with relevant national bodies and policy makers to incorporate wider use of CanRisk into routine breast cancer risk assessments.

https://www.nature.com/articles/s41416-024-02733-4

Aspirin and cancer: the emerging evidence

Professor Peter Elwood Honorary Professor, Cardiff University

There is a remarkable harmony between the effects of aspirin on the biological mechanisms of cancer metabolism and growth, and clinical evidence of reductions in cancer mortality and metastatic cancer spread.

Although aspirin increases the number of bleeds, the severity of bleeds attributable to aspirin is low, and the risk-benefit balance of aspirin appears to be favourable to aspirin.

COULD ASPIRIN STOP THE SPREAD OF COLORECTAL CANCER?

The recent study, carried out at the Chirurgia Generale Unit in Padova, Italy, involved 238 patients who were treated for colorectal cancer between 2015 and 2019. Among these, 31 patients were regular aspirin users, taking a daily dose of 100 mg.

The findings were promising. Regular use of aspirin was linked to a reduction in nodal metastasis, which is the spread of cancer to lymph nodes, and an increase in tumour-infiltrating lymphocytes. These lymphocytes, including T and B cells, play a crucial role in recognising and destroying cancer cells.

Could Aspirin Stop the Spread of Colorectal Cancer?

Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair–Deficient Colon Cancer

In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.)

(Neoadjuvant chemotherapy is delivered before surgery with the goal of shrinking a tumor or stopping the spread of cancer to make surgery less invasive and more effective.)

(DMMR =deficient DNA mismatch repair)

https://www.nejm.org/doi/full/10.1056/NEJMoa2400634

‘Gamechanger’ drug that ‘melts away’ tumours could replace surgery for bowel cancer

A “gamechanger” immunotherapy drug that “melts away” tumours dramatically increases the chances of curing bowel cancer and may even replace the need for surgery, doctors have said.

Pembrolizumab targets and blocks a specific protein on the surface of immune cells that then seek out and destroy cancer cells.

In the trial, funded by Merck Sharp and Dohme and sponsored by University College London, researchers recruited 32 patients with stage two or three bowel cancer and a certain genetic profile (MMR deficient/MSI-High bowel cancer) from five hospitals in the UK.

About 15 percent of patients with stage two or three bowel cancer have this particular genetic makeup.

Patients were given nine weeks of pembrolizumab, also known as Keytruda, before surgery instead of the usual treatment of chemotherapy and surgery, then monitored over time.

Results show 59 percent of patients had no signs of cancer after treatment with pembrolizumab, with any cancer in the remaining 41 percent of patients removed during surgery.

Dr Marnix Jansen, a clinician scientist at the UCL Cancer Institute, said more work needed to be done to assess pembrolizumab before it could be considered standard treatment.

https://www.irishtimes.com/health/2024/06/02/gamechanger-drug-that-melts-away-tumours-could-replace-surgery-for-bowel-cancer-say-doctors/

Let’s learn about how to prevent endometrial cancer!

https://engage.esgo.org/…/endometrial-cancer…/

In this webinar aimed at patients and patient advocates, we’ll discuss:

The psychological burden of a diagnosis (M Papageorgiou 🇬🇷)

Medical risk factors (Dr A Stepanyan 🇦🇲)

Genetic risks & prevention (Dr H El Hajj 🇫🇷)

with our co-chairs as moderators: Prof P Morice 🇫🇷 & K Hulscher

Note time is CEST

Patterns of cytotoxic T-cell densities in immunogenic endometrial cancers reveal a potential mechanism for differences in immunotherapy efficacy

A new study in BMJ Oncology suggests that Lynch Syndrome patients may be more susceptible to immunotherapy than sporadic MMRd endometrial tumours.

Objective To explore the impact of molecular subtype in endometrial cancer (EC) on CD8+T cell densities. Furthermore, this work will test the assumption that all mismatch repair deficient (MMRd) tumours are immunologically similar which would enable current trial data to be generalised to all MMRd ECs.

Conclusion These data indicate that CD8+T cell numbers and distribution is not equal between MLH1-methylated and confirmed LS ECs. This is relevant when interpreting current trial data looking to the application of checkpoint inhibition treatments in MMRd cancers.

https://bmjoncology.bmj.com/content/3/1/e000320

Ovarian cancer: identifying and managing familial and genetic risk—summary of new NICE guidance

https://www.nice.org.uk/guidance/ng241

What you need to know

  • Men and people born with male reproductive organs have a genetic risk of carrying a pathogenic variant associated with ovarian cancer and other cancers 
  • If a person had a direct-to-consumer genetic test and is reported to have a pathogenic variant for which NHS testing is offered, liaise with a regional NHS genetics service to discuss whether referral is appropriate
  • Refer for genetic counselling and testing people who have a first or second degree relative diagnosed with ovarian cancer, those from high risk groups, anyone identified through cascade testing, or those diagnosed with ovarian cancer linked to pathogenic variants
  • For women, trans men, and non-binary people born with female reproductive organs who are at increased risk of ovarian cancer, risk reducing surgery that is age appropriate for their pathogenic variant or family history is the most effective way to reduce the risk of ovarian cancer

Discover Available Cancer Support Options in Your Local Community

This directory is designed to help Healthcare Professionals guide cancer patients, their families, and friends to local cancer support services.

It also serves as a valuable resource for individuals living with and beyond a cancer diagnosis, and their loved ones, to discover the available cancer support options.

To access the Directory of Community Cancer Support Centres and Services click https://www.hse.ie/eng/services/list/5/cancer/profinfo/survivorship-programme/nccp-directory-of-community-cancer-support-centres-and-services.pdf

Innovative eMERGE study aims to address historical health inequities

Collaborations like the eMERGE IV study can help show how diverse population screening, better communication of test results and integration of genetic information into health risk reports can improve our understanding of how to reduce health risks for all.

No guidelines exist for proactive genetic testing to understand overall health risks in otherwise healthy individuals with no family history of disease, so comprehensive risk assessments that include genetic testing aren’t yet standard practice for most healthcare practitioners.

https://blog.invitae.com/innovative-emerge-study-aims-to-address-historical-health-inequities-0a20fd9c3691