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Jan 25, 2019 10:30PM
Shetland, the current F1 reports have "blurbs" about each biomarker. Maybe this is nothing new. I never received my 2016 F1 full report, only a few pages. Below is the blurb about microsatellite status/potential treatment strategies from my F1 test in December 2018, in case it is helpful. I am microsatellite stable and this is the blurb for someone who is stable but based on the write-up, it sounds mismatch repair deficiencies in breast cancer are microsatellite instable 51% of the time, and Lynch-syndrome related breast cancer was found to be microsatellite instable 60-85% of the time in one small study, although these stats don't distinguish between germline and somatic mutations.
I had the new F1 report done in order to enter the NCI MATCH basket trial for another genetic alteration (FGFR1). I started this process at the beginning of December, nearly 2 months ago, and was told today it will be another 3-6 weeks to get me cleared and that I was still at "Phase 0" and have two more stages to pass. I was originally told the whole process would take 2 weeks. Glad I insisted on going back on chemo while waiting. Great trial but the red tape is a joke.
POTENTIAL TREATMENT STRATEGIES
On the basis of clinical evidence, microsatellite stable (MSS) tumors are significantly less likely than MSI-high (MSI-H) tumors to respond to anti-PD-1 immune checkpoint inhibitors1-3, including approved therapies nivolumab and pembrolizumab4-5. In a retrospective analysis of 361 patients with solid tumors treated with pembrolizumab, 3% were MSI-H and experienced a significantly higher ORR compared with non-MSI-H cases (70% vs. 12%, p=0.001)6. Pembrolizumab therapy resulted in a significantly lower objective response rate (ORR) in MSS colorectal cancer (CRC) compared with MSI-H CRC (0% vs. 40%)5.
Similarly, a clinical study of nivolumab, alone or in combination with ipilimumab, in patients with CRC reported a significantly higher response rate in patients with MSI-H tumors than those without4.
FREQUENCY & PROGNOSIS
The frequency of MSI in breast cancer varies widely due to differences in patient characteristics and sample size. In a few studies of Lynch syndrome-related breast cancer patients with small sample sizes (n<10), MSI was observed in 60%-85% of patients7-11. However, no MSI was observed in a few larger scale analysis of breast cancer samples12-13.
Moreover, MSI was reported in 51% of patients with MMR deficient breast cancer14.
Furthermore, a prospective study observed increased MSI following chemotherapy treatment, and MSI is associated with incidence of secondary tumors15.
Microsatellite instability (MSI) is a condition of genetic hypermutability that generates excessive amounts of short insertion/deletion mutations in the genome; it generally occurs at microsatellite DNA sequences and is caused by a deficiency in DNA mismatch repair (MMR) in the tumor16. Defective MMR and consequent MSI occur as a result of genetic or epigenetic inactivation of one of the MMR pathway proteins, primarily MLH1, MSH2, MSH6, or PMS216-18. The tumor seen here is microsatellite-stable (MSS), equivalent to the clinical definition of an MSS tumor: one with mutations in none of the tested microsatellite markers19-21. MSS status indicates MMR proficiency and typically correlates with intact expression of all MMR family proteins16,18,20-21.
Chart your own course. Dx at 30. Dx with mets at 38 while pregnant - extensive liver & bone involvement. Currently on Enhertu & XGeva. ER+/PR+, HER2-low (IHC equivocal, +2/FISH negative). Y90 liver radioembolization in 2018.
9/2006, IDC, Right, 1cm, Stage IIB, Grade 3, 1/16 nodes, ER+/PR+, HER2- (FISH)
9/22/2006 Mastectomy: Left, Right
11/5/2006 Adriamycin (doxorubicin), Cytoxan (cyclophosphamide), Taxotere (docetaxel)
3/15/2007 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
12/2014, IDC, Stage IV, metastasized to bone/liver/other, Grade 3, ER+/PR-, HER2-
12/26/2014 Prophylactic ovary removal
12/26/2014 Aromasin (exemestane), Faslodex (fulvestrant)
6/18/2015 Ibrance (palbociclib)
3/10/2016 Xeloda (capecitabine)
5/13/2017 Aromasin (exemestane)
5/13/2017 Afinitor (everolimus)
8/18/2017 Abraxane (albumin-bound or nab-paclitaxel)
3/23/2018 Doxil (doxorubicin)
4/26/2019 Navelbine (vinorelbine)
4/26/2019 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
11/26/2019 Gemzar (gemcitabine)
8/24/2020 Faslodex (fulvestrant)
8/24/2020 Piqray (alpelisib)
10/1/2020 Enhertu (fam-trastuzumab deruxtecan-nxki)