Will 30% of Early Stage (1-IIIA) go on to metastasize??
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Hi everyone...just want to add that my doc at a major NYC university hospital told me that 50 percent do not complete the 5 recommended years of anti hormone therapy due to side effects. He said that includes both Tamoxifen and aromatase inhibitors. This is the reason I have always said that we need better treatment options!
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Platelets and Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41869...0 -
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From SABC 2017:
December 6, 2017—San Antonio, Texas— Patients with metastatic breast cancer have been shown to exhibit frequent mutations in high- and moderate-risk breast cancer genes.
This outcome of a registry review of prospectively collected data was reported at the 2017 San Antonio Breast Cancer Symposium, from December 5 – 9.
Peter A. Fasching, MD, of Erlangen University Hospital, Erlangen-Nuremberg, Germany, explained that new treatment strategies for metastatic breast cancer are mainly driven by therapies against specific targets.
BRCA mutations are one of the few established actionable targets, with PARP inhibitors and platinum-based therapies showing high efficacy in metastatic breast cancer. Hereditary cancer testing panels are now used broadly to identify individuals with BRCA1/2 mutations who may benefit from these therapies.
Many of these panels also contain other predisposition genes involved in BRCA-related DNA repair pathways, though the clinical relevance of mutations in these genes remains unclear.
Dr. Fasching and colleagues set out to describe the mutation rates of BRCA1/2 and panel-based predisposition genes, as well as associated clinical characteristics of individuals with these mutations.
The PRAEGNANT metastatic breast cancer registry is a prospective registry for patients with metastatic breast cancer that focuses on molecular biomarkers. Patients who receive any therapeutic regimen are eligible for the registry.
Germline DNA was collected at study entry and genotyped for 37 genes predisposing to cancer, including BRCA1 and BRCA2. The frequency of mutations in each gene was determined, and associations between mutations and patient and tumor characteristics, metastatic pattern, and overall survival assessed.
Mutations in established high- (odds ratio >5.0) and moderate-risk (odds ratio >2.0) breast cancer genes (BRCA1/2, PALB2, CHEK2, ATM, RAD51D, BARD1, and MSH6) were seen in 123 of 1462 tested patients with metastatic breast cancer (8.4%). BRCA1 and BRCA2 mutations were seen in 1.4% and 2.9% of patients, respectively.
The most frequently mutated non-BRCA panel genes were CHEK2, PALB2, and ATM, found in 2.8%, 0.8%, and 0.6% of patients, respectively. Mutation frequency varied with regard to patients who developed brain metastases, visceral metastases or bone-only metastases.
BRCA1 or BRCA2 mutations were seen frequently in patients with brain (5.3%) or visceral metastases (5.2%), but were present in only 2.5% patients with bone only metastases and 1.5% of patients with lesions in other locations. Panel genes were equally distributed among all metastatic patients.
PALB2 mutations (n=11) were seen only in patients with brain (1.9%) and visceral metastases (0.9%), but not in patients with bone metastases or other locations. A total of 36.4% (n=4) of all patients with PALB2 mutations developed a brain metastasis.
When adjusted for other prognostic factors in metastatic breast cancer, a mutation (all genes) was associated with an unfavorable prognosis (hazard ratio 1.50, 95% confidence interval 1.04 to 2.30, P = .03).
The frequency of mutations was similar according to lines of therapy. All other associations with molecular subtypes and risk factors were similar to those of primary breast cancer cases.
Dr. Fasching concluded that mutations in high- and moderate-risk breast cancer genes were observed at a frequent rate in patients with metastatic breast cancer.
The frequency was substantially higher than the 4% to 5% frequency of mutations observed among unselected patients with primary breast cancer, but consistent with recent results of studies of patients with metastatic prostate cancer.
Patients with brain and visceral metastases exhibited the highest rates of BRCA mutations. The results suggested that PALB2 mutations may be more frequent in patients with brain metastases.
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Molly, I felt sick reading this earlier today.
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Hopeful, me too but then it justified my decision to fire my MO and get a new one.
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Makes me sick to think of since I have a palb2 mutation
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Lovinggrouches - Do you actually have a deleterious mutation or is it strictly a VUS? If it makes you feel any better, most VUS are eventually reclassified as benign.
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hopeful82014...how do you find out if it had been reclassified
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Waiting for a reclassification of a VUS is generally a very long wait. There are thousands of them and building a meaningful database of these genetic variations appears not to be a priority because evidence of their known effects is so slim.
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ThinkingPositive - That's a good question! Ideally, your genetic counselor should update you (and/or the ordering physician) of any changes in the status of a VUS. However, that doesn't always happen, for a variety of reasons.
You could designate someone else that you know you will see on an on-going basis, such as your MO or PCP to be notified in the event of changes.
The easiest way is to call the company that handled your genetic testing. They have staff who work specifically with patients and are very happy to discuss such issues.
As traveltext stated, it can be a long, long time before a VUS is reclassified so probably checking no more often than once every year or two is appropriate.
If you have a VUS you can check into participation in studies such as the PROMPT study which is collecting information to better understand the results of both VUS and deleterious mutations:
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Molly, thank your for the post from San Antonio about the PRAEGNANT study. Can you tell me how to directly access what you posted, and the name of the paper? Or was it just a talk? The MSH6 mutation has not been considered a breast cancer gene in the past, though I saw one small study that suggested it could be. This is important for me to understand. It may help answer the question, "What the hell happened?"
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Mine is VUS. I am participating in the prompt study
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Interesting, Re: PROMT study. I’d never heard of it. I contacted them with the results of my BRCA test from a few years ago and they said I am eligible and should participate. What exactly does participating in this entail? Many thanks!!
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JuniperCat, here's a link to more info:
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Thank you!
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If I remember correctly, I sent info on family tree of breast cancer relatives, filled out a survey or two, sent a copy of genetic results and did sputum specimen
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SABCS 2017: Circulating tumour cells may predict late recurrence in HR-positive breast cancer patients
08 Dec 2017
Among patients with hormone receptor (HR)-positive HER2-negative stage 2-3 breast cancer without clinical evidence of recurrence, those who had circulating tumor cells (CTC) detected in blood five years after diagnosis had an increased risk for late recurrence of breast cancer, according to data presented at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.
"We found that a single positive CTC assay result five years after diagnosis provides independent prognostic information for late recurrence," said Joseph A. Sparano, MD, associate director for clinical research, Montefiore Einstein Center for Cancer Care, Albert Einstein Cancer Center, New York. "This provides proof of concept that liquid biopsy-based biomarkers may be used to stratify risk for late recurrence and possibly inform treatment or clinical trial options."
Despite advances in breast cancer treatment in recent years, many women still have late recurrent disease five years or more after the initial diagnosis. HR-positive breast cancers, which make up more than half of all breast cancer cases, have an increased risk of late recurrence, noted Sparano.
"Biomarkers for late recurrence that may help guide therapy are needed," he stressed.
Participants of Sparano's study were previously enrolled in a clinical trial which assessed the addition of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, to chemotherapy as adjuvant treatment following surgery.
Sparano and colleagues measured CTCs in blood samples from patients using the CELLSEARCH CTC assay between 4.5 and 7.5 years after an initial diagnosis of HER2-negative stage 2-3 breast cancer.
No patients had clinical evidence of recurrence at the time of enrollment.
Of patients with HR-positive breast cancer, 4.5 percent had recurrence of the disease; this compares to a recurrence rate of 0.5 percent in the HR-negative group.
Of the 546 patients enrolled in the study, 4.8 percent had a positive CTC assay result.
Among patients with HR-positive breast cancer, 5.1 percent had a positive CTC result; among those with HR-negative disease, 4.3 percent had a positive CTC result. After a median follow-up of 1.6 years, a positive CTC assay result was associated with a nearly 20-fold increased risk of breast cancer recurrence in patients with HR-positive disease.
The positive predictive value of a positive CTC assay for recurrence by two years in patients with HR-positive disease was 35 percent, and the negative predictive value for patients in this cohort was 98 percent.
A positive CTC assay was not associated with recurrence in the HR-negative group.
Sparano commented that these results were somewhat unexpected.
"We were surprised to see that 5 percent of patients had CTCs about five or more years after their initial diagnosis," he said. "Although we were expecting that CTC-positive patients would have a higher recurrence rate, we weren't expecting the risk of recurrence to be this high after a relatively short period of time."
"This study provides strong evidence of the clinical validity of the CTC assay as a prognostic biomarker for late recurrence in HR-positive breast cancer, which accounts for about one-half of all recurrences," Sparano said. "Utilizing the CTC assay for prognostic analysis may aid in a more accurate identification of patients who would most benefit from extended adjuvant endocrine therapy or other treatment options," he noted.
Next steps include studying how a single negative CTC test or serial negative tests could serve as a negative predictive marker that may allow sparing of extended adjuvant endocrine therapy beyond five or more years. Limitations of the study include short follow-up after the CTC assay, with an average time of 1.6 years.
Sparano noted that additional follow-up is required, and that further study will be necessary to determine the clinical utility of the CTC assay in this setting.
Watch the press conference for more.
Source: SABCS
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thanks for the info. I will look into this study.
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017.
ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.
https://www.ncbi.nlm.nih.gov/pubmed/29042797
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This study echoes what i have been told. I am now heading into year 6 since diagnosis.
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Here’s the cancer statistics 2018.I don’t know where to put it so I’ll put it here.
http://onlinelibrary.wiley.com/doi/10.3322/caac.21...0 -
Wow marijen - That is quite a report. Thanks so much for posting. Sobering. Numbers were higher than what I thought. Ugh. Carpe Diem.
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marijen...about you post on recurrence after 5 years on endocrine therapy. That means that it should be 10 years for those of us that fall into that category. I assume that’s me. 1 node positive. Grade 3. And my MO said the further out I get from diagnosis the less likely!!!
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ThinkingPositive, that's what my MO said for me as well. 1 node Grade 3. Because of the grade 3 it is most likely to show up in the first 5 maybe 10 years and then go down over time. I was turning 45 around my diagnosis and although she said she could never say cured or all clear she did say that if I hadn't had a reoccurance by 65ish I would "most likely" be clear. Who knows what they'll figure out in the mean time. Now I just have to decide on the whole ovary removal thing to slightly up my chances. Ugh 😑
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Remember that science has changed. Long term statistical outlooks mean that the original ocurrence and treatment were x years old.
Have hope and keep fighting.
My oncologist told me that after being a woman (huh...not changing that), the next greatest risk is being overweight, because fat produces estrogen. I think there's so much we can do with diet and exercise and just healthy living nowdays that can reduce our risk. And they are coming up with new treatments all the time. Maybe in 10 years after a mastectomy, we will have stem cell implants that can regrow healthy breast tissue. A girl can hope, right?
Hugs,
Holly
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I am just over 4 years on blockers. At my recent MO visit a couple weeks ago I wanted to discuss 5 vs 10 years on blockers but she wouldn't go there and said we have time and science is changing all the time. It was her thought that in the next year more would be known. I really wanted a plan and time to mull things over but also encouraged that research on all of this is ongoing and progressing at a fast pace. Yes Holly, "a girl can hope". She too is unconvinced as to the accuracy of the BCI test at this juncture.
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TWills.... I had both of mine out plus Fallopian tubes. No big deal as I had already gone through menopause years before being diagnosed at 58. I had a small cyst on one ovary that we were following up on every 6 months. Got tired of that and a few months after finishing chemo I wanted them out. Recovery was no big deal.
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5 to 10 sounds like a prison sentence to me, I got out at 2.5 due to eyesight problems. There is more information at How Many Are Doing Aromastase Therapy for 10 Years
https://community.breastcancer.org/forum/78/topics...Holly Dolly, yes hope is in abundance. I am hoping for growing a new lumbar 1.. and for better treatment that doesn’t require depressing our hormones.
And fighting the weight batlle daily.
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I've just started Tamoxifen two months ago and doing fine so far so I hate to mess with that, seems the newest conference data that my MO went to last month said ovaries out(in my case, pre menopause) with AI's have a slightly better % of reducing reoccurance. It's a small % and I don't want worse side effects so it's a gamble for sure. Side effects are my concern.Again, I say she said this for my case.
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