ICARE Social Media Post July 2020

BRCA1/2 and Other Gene Carriers with Breast Cancer Don’t Always Receive Recommended Treatment

BRCA1/2 and other gene mutation carriers with early stage breast cancer are not always receiving cancer treatment as recommended by national guidelines.

Even though more and more people have been tested for hereditary cancer over the years, using this information accurately to guide treatment has not been as successful.

These findings highlight the need for using this information better to help guide appropriate breast cancer treatment, including radiation treatment and chemotherapy.

Check out the full article at https://jamanetwork.com/journals/jamaoncology/fullarticle/2760433.

ICARE Newsletter Winter 2020

Updates to National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic

There were significant updates and restructuring of the guidelines, with some highlights included below:

  • Substantial reorganization of the guidelines as follows:
    • Now organized by organ site, rather than primarily by certain high penetrance genes
    • Focused efforts to simplify genetic testing criteria
    • Only one flow diagram included, to outline the ‘genetic testing process’
  • Following scenarios now outlined:
    • Situations in which genetic testing may have low yield
    • Situations where referral to a genetics expert is recommended
  • PALB2: Recognized as a high penetrance gene, for which discussion of risk-reducing mastectomy is appropriate
  • BRCA1/2: Prostate cancer screening to be initiated at age 40
  • Pancreatic screening guidance included:
    • STK11 starting at age 30-35
    • CDKN2A starting at age 40
    • BRCA1/2, ATM, MLH1, MSH2, MSH6, EPCAM, PALB2, or TP53: Only if there is a close family member with pancreatic cancer

For the complete updated versions of the NCCN guidelines, please visit NCCN.org

Follow this link to view our social media post: https://tinyurl.com/ICARE2019124

Full press release available at: https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1790

ICARE Social Media Post December 2019

Updates to National Comprehensive Cancer Network (NCCN) Genetic/Familial Breast, Ovarian, and Pancreatic Guidelines (V1.2020)

We are excited to share the latest version of the NCCN Genetic/Familial Breast, Ovarian and Pancreatic Guidelines (V1.2020), which were just updated. Some of the changes made include:

  • PALB2 was added as a high penetrance gene (similar to BRCA1, BRCA2, CDH1, PTEN and TP53)
  • It is appropriate to consider risk reducing mastectomy for cancer risk management (as well as high risk screening through mammograms and MRIs).
  • The age at which screening for prostate cancer among men with a BRCA2 mutation was lowered from 45 to 40.
  • Pancreatic cancer screening:
    • Individuals with STK11 (which leads to Peutz-Jeghers Syndrome) or CDKN2A mutations has been added
    • ONLY a consideration in patients with a mutation in BRCA1/2, ATM, MLH1, MSH2, EPCAM, PALB2, and TP53 IF there is a close family member (first or second degree relative on the same side of the family) with pancreatic cancer
  • The guidelines also outline situations in which there is a very low chance of finding a mutation (i.e., pathogenic/likely pathogenic variant).

To see the full version of the guidelines, go to nccn.org, where they will ask you to create a username and password (which anyone can do), after which you will be able to view whichever guidelines you want. Check it out at https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1790!

ICARE Newsletter Summer 2019

Community Spotlight

Life was great at 45. I had nothing more than a few headaches and was a tad overweight. After a friend was diagnosed with breast cancer, I realized I had not had a mammogram in a couple of years, so I scheduled an appointment. One mass was found, but it was benign and nothing to worry about. The mass continued to grow, and again, a biopsy confirmed it was benign. The mass was removed, and I went on with my life. A few months later, I returned for a follow-up appointment. It felt like a blow to my chest as the doctor confirmed I had a rare malignant phyllodes tumor in one breast. Because of the rarity of this type of cancer, I was offered genetic testing. A few months later, I was diagnosed with Li-Fraumeni syndrome (due to a TP53 mutation), a rare condition that greatly increases the risk for many types of cancers.

I have three children ages 11, 22, and 27. My 11-year-old was diagnosed with autism at age 3, which has prepared me to advocate like no other. Although there is so much more to my story, when faced with challenges, I prefer to come through and share the answers I have collected throughout my journey. I’m just starting, but here are a few tips I have used to cope:

  1. Brainstorm your thoughts in a journal. I have learned there are so many things I can’t control, but so many more that I can.
  2. Get your life in order and encourage your family and friends to do the same. With or without Li-Fraumeni syndrome, we are all guaranteed a death which can happen at any moment. As crazy as it sounds, while journaling, I realized that death was not my real fear. My real fear was leaving my son, and what his life would look like if I was not here to take care of him. Insurance policies, wills, trusts, and written expectations for my son are no longer something just on a to-do list.
  3. Get organized. I’m still figuring this out, but the appointments and test results can take over your life quite literally. Getting a calendar and establishing systems that work for you is a must.
  4. Research solutions and take an active role in your care. Ask questions no matter how silly they may seem. Always ask, “Is that the best we can do, and what are my other options?”
  5. Take your time when making decisions. Never allow anyone to pressure you into making a decision. Sometimes you have to take a step back and seek wise counsel.
  6. Create a “worry” section in your journal. As things pop up in my mind, I write them in the “worry” section of my journal and tell those thoughts that we can talk about them later during my worry time. “Worry time” is time I set aside to worry so that my day is not consumed with worry, which helps me stay focused on positive things. Typically, by the time “worry time” comes around, I have either found a solution, or I’m over it!
  7. This probably should have been number 1 on the list but seek therapy. A few weeks in I realized the thoughts about “what if” were consuming me. Depression is real. Get a good therapist. It may take several sessions with several therapists but talking it out can be a game changer.

Hope this helps because I’m out of space. Sending great vibes and love your way!

―ICARE participant, Angela Watson, from Memphis, Tennessee

ICARE Newsletter Summer 2019

Expanding Our Thinking About Cancer Risks in TP53 Mutations and Li-Fraumeni Syndrome

Since expanded genetic testing has become available through multigene panel tests, studies have suggested that many people identified to have TP53 mutations do not have a typical personal or family history, which is usually seen with Li-Fraumeni syndrome (LFS). A recent study looking at over 300 individuals with TP53 mutations (identified through multi-gene panel testing) suggested that the level of cancer risks was dependent on the type of mutations within the TP53 gene. Specifically, those with a loss-of-function mutation (i.e., causing the protein produced from the TP53 gene to lose its function) tended to have stronger, more classic family histories suggestive of LFS, compared to those with other types of mutations (i.e., dominant-negative missense, other missense, splice site, or in-frame deletion). Although these findings require confirmation through other studies, this type of information may eventually become very helpful for genetic counseling by refining cancer risks and guiding follow-up care among individuals with TP53 mutations.

Rana, et al. Genet Med. 2019 May. PMID: 31105275.

ICARE Newsletter Summer 2018

Inherited Leukemias: The Importance of TP53/Li-Fraumeni Syndrome and Other Genes

It has long been established that the risk for developing leukemia in childhood is high among individuals with Li-Fraumeni Syndrome; however, better understanding the characteristics of leukemia among these individuals is important to guide treatment approaches. In a study of children with Acute Lymphocytic Leukemia (ALL), those with a germline TP53 mutation (compared to those without a mutation) were older (median age of 15.5 years, compared to 7.3 years), were at a much higher risk of second cancers (25.1% versus 0.7%), and were more likely to have hypodiploid ALL (65.4% versus 1.2%), with poorer outcomes.1 This information may be important to guide treatment among these individuals, including type and timing of treatment.

In addition to Li-Fraumeni Syndrome, there are several other conditions that are associated with inherited susceptibility to leukemia among individuals of all ages, including those associated with bone marrow failure syndromes, those in which myelodysplastic syndrome is seen before the onset of leukemia, and those with primarily a leukemia risk.2 Patients with inherited hematologic malignancy syndromes may present without classic clinical signs of a particular familial syndrome or even a family history.3 As more patients with inherited forms are diagnosed, there remains a need for developing evidence-based recommendations because current recommendations are primarily based on expert consensus.4

1Qian M, et al. J Clin Oncol. 2018 Feb 20. PMID: 29300620.
2McReynolds LJ, et al. Hematology Am Soc Hematol Educ Program. 2017 Dec 8. PMID:29222262.
3Furutani et al. J Clin Oncol. 2017 Mar 20. PMID: 28297620.
4Godley LA, et al. Blood. 2017 Jul 27. PMID: 28600339.

ICARE Newsletter Summer 2018

New Data to Suggest Additional Genes Associated with Breast and Ovarian Cancer

A recent study reported on cancer risks among over 10,000 cancer patients across the United States who had genetic testing. Findings suggest breast cancer risks were associated with ATM, CHEK2, and PALB2, as expected; but an association was also found with MSH6 (in line with other recently published data, as outlined in another article in this newsletter). Regarding ovarian cancer risks, associations were found with MSH6 and RAD51C, as previously reported; however, risks were also reported with TP53 and ATM. These data provide new insight on both previously confirmed well-established breast and ovarian cancer genes, while implicating additional genes not currently established to be associated with these cancers.

Lu H, et al. JAMA Oncol. 2018 Aug 16. PMID: 30128536.

ICARE Newsletter Winter 2018

Updates to NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian Guidelines

(Version 1.2018, posted Oct. 3, 2017)

  • Metastatic prostate cancer was added as an indication for evaluation and testing for the BRCA1 and BRCA2 genes
  • Among BRCA1, BRCA2, TP53 and PTEN carriers, women between ages 25-29 may consider having an annual mammogram with consideration of tomosynthesis if a breast MRI is not available.
  • Among female BRCA2 carriers, language regarding age of risk-reducing salpingo-oophorectomy (surgical removal of one or both ovaries and fallopian tubes) was updated to indicate that it may be delayed to age 40-45
  • The table for other inherited breast and ovarian cancer genes was updated per the recent advances.

For the complete updated versions of the NCCN Guidelines, please visit NCCN.org

ICARE Newsletter Winter 2018

Study Suggests Inherited Cancer Genes Are Important in Pancreatic Cancer

In a recent study which included over 800 patients with pancreatic ductal cancer, inherited cancer gene mutations were found in a much higher proportion than expected. Almost 5% of these patients had mutations identified in inherited cancer genes, the majority of which were in genes thought to be associated with pancreatic cancer (including BRCA2, ATM, BRCA1, PALB2, MLH1, CDKN2A, and TP53).  Those that had mutations identified tended to be younger on average, however most did not have a family history of cancer that would suggest the presence of inherited mutations. These findings demonstrate that a meaningful number of patients with inherited risk for pancreatic cancer will be missed if relying on only family history. With the development of drugs to target cancers which develop among those with inherited disease, this study shows that relying too heavily on family history may lead to missing patients who would otherwise be eligible for these targeted treatments.

Shindo et al. J Clin Oncol. 2017 Oct 20;35(30):3382-3390. PMID: 28767289.

ICARE Newsletter Winter 2018

Advances in Cancer Screening Among Li-Fraumeni Syndrome Patients

Several research groups from around the world that have conducted cancer screening among patients with Li-Fraumeni syndrome and a germline TP53 mutation have recently reported on their observations. Specifically, the National Cancer Institute group demonstrated that screening inclusive of rapid total body MRI detected cancers at an early stage,1 similar to findings published through other recent smaller studies.2,3 Collectively, these findings demonstrated the extensive screening advised for many Li-Fraumeni patients is feasible; however, some of this screening may lead to false positives (i.e., a positive finding on a cancer screening test that ends up not being cancer) as well as cancer overdiagnosis.Through a recent effort to look at whole body MRI in Li-Fraumeni syndrome patients across several previously published studies, data suggested that this screening test may be clinically useful and an important part of cancer risk management. Additionally, we recently published an article focused on ICARE participants with a germline TP53 mutation, who were identified based on a multi-gene panel test.6 We found that many of these individuals did not have a family history that would identify them as having Li-Fraumeni syndrome, which suggests that cancer risk in some of these ‘non-characteristic’ families may not be as high as those with a classic family history of Li-Fraumeni syndrome. This brings up the question about what screening is most appropriate for them. Overall, these articles all highlight the need to generate more evidence to refine screening practices among individuals with Li-Fraumeni Syndrome.

1Mai et al. JAMA Oncol. 2017 Dec 1;3(12):1640-1645. PMID:28772286.
2Ballinger et al. JAMA Oncol. 2017 Dec 1;3(12):1735-1736. PMID:28772290.
3Ruijs et al. JAMA Oncol. 2017 Dec 1;3(12):1733-1734. PMID:28772294.
4Asdahl PH, Ojha RP, Hasle H. JAMA Oncol. 2017 Dec 1;3(12):1645-1646. PMID:28772307.
5Ballinger et al. JAMA Oncol. 2017 Dec 1;3(12):1634-1639.PMID:28772291.
6Pal et al. South Med J. 2017 Oct;110(10):643-648. PMID:28973705.

ICARE Newsletter Summer 2017

What Are New and Subsequent Cancer Risks Among Patients with Li-Fraumeni Syndrome?

Although individuals with Li-Fraumeni Syndrome (LFS), due to mutations in the TP53 gene, have a very high lifetime risk of cancer, risks of initial and subsequent cancers are not well defined. Through a group of patients with the classic form of LFS, researchers at the National Cancer Institute estimated their cancer risks. They evaluated a total of 286 individuals with TP53 mutations from 107 families, and found of women 50% had developed cancer by age 31 and of men 50% had developed cancer by age 46. This suggests that on average women with LFS tend to develop cancer earlier than their male counterparts. For women, cancer risk was the contributing highest after age 20, mainly due to high risks of breast cancer. This differed in men, where the risk was highest in childhood and later adulthood. Among both sexes, almost 100% of individuals had developed cancer by age 70. Cancer risks outlined by type of cancer developed by age 70 among women and men with LFS are shown in the table below.

Cancer Type

Cancer Risks by Age 70



Breast cancer



Soft tissue sarcoma



Brain cancer






Of individuals who developed cancer, about half went on to develop at least one more cancer after an average timeframe of 10 years.  Furthermore, having been diagnosed with one cancer did not lower their risk of developing a subsequent cancer.  The new information from this study helps to refine cancer risk estimates among those with LFS, which is needed to guide their cancer risk management strategies.

Mai et al. Cancer. 2016 Dec 1;122(23):3673-3681. PMID: 27496084.

ICARE Newsletter Summer 2017

Breast and Ovarian Cancer Associations for Genes Tested Through Multi-Gene Panels

As testing for multiple genes at the same time (“multi-gene panel testing”) has become increasingly available with tremendous advances in genetic testing technology, it has become critical to evaluate and refine cancer associations and levels of risk for many of these genes now tested. Through a commercial laboratory database of almost 100,000 results of multi-gene panel testing, associations between mutations in specific genes with breast and ovarian cancers were evaluated. Findings indicated that 8 genes were associated with breast cancer and 11 genes were associated with ovarian cancer. Most had previously been confirmed in association with breast cancer, including ATM, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53. An additional newer gene, BARD1, was also found to be associated with breast cancer in this dataset, but remains a gene for which data continues to emerge to help determine whether a true association with breast cancer exists.  Similarly, for ovarian cancer, most genes identified to have an association were consistent with data from prior studies, including BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, STK11, RAD51C, and RAD51D. Additional genes that were shown to have an association with ovarian cancer in this dataset included ATM and NBN, however additional research is needed to determine if an association with ovarian cancer truly exists. Ultimately, there remains a great need to continue to evaluate cancer risks for inherited genes for which we have limited information about level of risk and types of associated cancer.

Kurian et al. JCO Precision Oncology. 2017 :1, 1-12

ICARE Newsletter Summer 2016

Surveillance Among Individuals with Li-Fraumeni Syndrome (LFS): An 11 Year Follow-Up Study

Results from the original screening protocol for LFS1 were recently updated following collection of 11 years of follow-up data.2 Through this study, 89 patients with LFS were given the option of a clinical surveillance protocol consisting of a physical examination as well as frequent biochemical and imaging studies. Forty asymptomatic tumors were detected in 32% of the TP53 mutation carriers who chose clinical surveillance. Overall survival was much higher in the surveillance group (almost 90%) compared to the non-surveillance group (~60%). These data imply benefits from ongoing comprehensive cancer surveillance with early detection of tumors with suggestions that overall survival may be improved. 

1Villani et al. Lancet Oncol. 2011 June. PMID: 21601526.
2Villani et al. Lancet Oncol. 2016 Aug 5. PMID: 27501770.

ICARE Newsletter Winter 2016

Improving Our Understanding of Cancer Risks Among Individuals with Li-Fraumeni Syndrome

A recent study from France included over 400 patients with Li-Fraumeni Syndrome (all of whom had an inherited TP53 gene mutation). Cancer types among children and adults differed, with the main cancer types among children being osteosarcomas, adrenocortical carcinomas, central nervous system (CNS) tumors and soft tissue sarcomas; whereas among adults, the main cancer types were breast cancer and soft tissue sarcomas. 

The study also evaluated whether the type of mutation was associated with a specific presentation of cancer.  What they found was that average age at which cancer presented was substantially lower among those who had a ‘dominant negative’ missense mutation (21.3 years) compared to those with all types of loss-of-function mutations (28.5 years) or genomic rearrangements (35.8 years).  With the exception of children with adrenocortical carcinoma, most affected children had dominant-negative missense mutations.

Among women ages 30 or younger with breast cancer, TP53 mutations were detected in 6%.  Breast cancer pathology reports were evaluated in a group of TP53 carriers, and showed that 55% were HER2 receptor positive and 37% were triple positive (i.e., ER, PR and HER2 receptor positive).  Among women with breast cancer and a TP53 mutation, the development of contralateral breast cancer (cancer in the opposite breast) was very high at 31% compared to an estimated 10% contralateral breast cancer risk among women in the general population.

There was a high rate (43%) of multiple primary cancers among TP53 mutation carriers, the majority of which were cancers that developed following an initial cancer diagnosis.  Treatment records were available on a subset of patients who received radiation treatment for their first tumor which showed that 30% developed secondary tumors in the radiation field, within 2-26 years (mean, 10.7 years) following their initial cancer treatment.

With the increasing use of multi-gene tests, mutations in TP53 are unexpectedly being identified in individuals without a family history characteristic of Li-Fraumeni Syndrome.2

Consequently, clinicians and researchers are pursuing efforts to better understand the expanding cancer risks and how cancer presents among some of these individuals who are unexpectedly found to have a TP53 mutation, which is needed to further tailor their medical care.

1Bougeard G et al. J Clin Oncol. 2015 Jul 20;33(21):2345-52. PMID: 26014290
2Kamihara J,et al. Hum Mutat. 2014 Jun;35(6):654-62. PMID: 24706533

ICARE Newsletter Summer 2015

2015 NCCN Clinical Practice Guideline Update

Breast and Ovarian Management Based on Genetic Test Resultsa


Recommend Breast MRIc
(>20% lifetime risk of breast cancerd)

Recommend Risk-reducing salpingo-oophorectomy Discuss Option of Risk-reducing mastectomy
Intervention warranted based on gene and/or risk level ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, STK11, TP53 BRCA1, BRCA2, Lynch syndromee BRCA1, BRCA2, CDH1, PTEN, TP53
Insufficient evidence for











Note: To access full guidelines document, refer to www.nccn.org

aOther genes may be included in mutli-gene testing. cSee NCCN Guidelines for Breast Cancer Screening and Diagnosis.  dMay be modified based on family history or specific gene mutation. eSee NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal.