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Dec 8, 2020 07:48AM
buttonsmachine
wrote:
I stumbled upon this article, and thought it was a very good (but sobering) article about the mechanisms of metastatic recurrence in breast cancer. This article covers the how, why, when, where, and what we can do about it.
I had my first metastatic recurrences this year. I went from NED after a local recurrence to innumerable metastatic lesions in only a few months. That blindsided me, and hit me like a freight train. In these situations it sometimes helps me to understand the science and the mechanisms behind why and how these things happen. I thought this article might be helpful for others, too.
Riggio, A.I., Varley, K.E. & Welm, A.L. The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-01161-4
Here are a few key takeaways from the conclusions sections, but the whole article is really interesting:
"[O]ur current understanding of metastatic dormancy, metastatic evolution, acquired resistance and metastatic niches suggests that detecting and treating recurrence earlier might be our best opportunity to improve patient outcomes.
Despite metastatic disease being the main cause of death in cancer patients, knowledge about the biology of this lethal process is lacking. However, with advances in genomic sequencing technologies and accumulating data in favour of the predominance of the parallel model over the linear model of dissemination, four important lessons have been learned. First, in most patients who will experience recurrence, metastases are already present at the time of diagnosis. Second, despite their genomic similarity to the trunk of the tumour's evolutionary tree, metastases are distinct biological entities, containing important phenotypic differences compared with their primary source. Third, metastases, as well as primary neoplasms, are subject to evolution dictated by pharmacological pressure, tissue-specific environments and cellular plasticity. Finally, some micrometastases might exist in a non-proliferative, dormant-like state for months to decades.
Altogether, these data have significant clinical implications. First, attempts to prevent initial metastatic dissemination might hold little therapeutic benefit—even though early detection and treatment of most primary breast tumours is curative, tumours that are 'born to be bad' probably disseminate prior to diagnosis. Next, caution must be taken when using primary tumours as a proxy for clinical decisions on systemic therapies to prevent or treat metastatic disease, unless little divergence between paired lesions is observed. In this respect, non-invasive liquid biopsy biomarker assays could help to identify molecular changes in metastases. In addition, an urgent need exists to assess the phenotypic properties of DTCs in their native states, in order to understand how some DTCs, but not others, contribute to metastatic recurrence. Finally, it might be possible to exploit tumour dormancy in some, but probably not all, cases as a window of opportunity to tackle MRD and/or prevent metastatic relapse (Table 1).
Future directions should be centred on identifying dangerous versus indolent DTCs and finding new DTC drug targets, while also using modern imaging and biomarker assays to accurately determine who needs such therapy, in order to avoid overtreatment. Importantly, all of the above strategies—prevent, reverse, prolong and eradicate dormancy (Table 1)—will require the development and use of more clinically relevant models and human samples, as well as clinical trials of new 'intensive' follow-up monitoring programmes. With progress in these areas, it is hoped that new knowledge will converge in the near future to prevent recurrences and deaths from cancer."
Diagnosed at 32. Local recurrences one year later. Now dealing with MBC.
Dx
8/2016, IDC, Right, Stage IA, Grade 3, 0/2 nodes, ER+/PR+, HER2-
Surgery
10/1/2016 Lumpectomy: Right; Lymph node removal: Sentinel
Chemotherapy
10/31/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel)
Radiation Therapy
2/1/2017 Whole-breast
Hormonal Therapy
3/31/2017 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
Dx
10/2017, IDC, Right, Grade 3, 2/12 nodes, ER+/PR+, HER2-
Surgery
11/1/2017 Lymph node removal; Mastectomy: Right
Chemotherapy
11/30/2017 AC
Surgery
3/31/2018 Lymph node removal; Mastectomy: Right
Radiation Therapy
4/30/2018 External: Lymph nodes, Chest wall
Chemotherapy
6/30/2018 Xeloda (capecitabine)
Hormonal Therapy
7/30/2018 Zoladex (goserelin)
Hormonal Therapy
2/1/2019 Aromasin (exemestane)
Hormonal Therapy
9/30/2019 Faslodex (fulvestrant)
Dx
8/2020, IDC, Stage IV, metastasized to bone/liver/other, Grade 3, ER+/PR+, HER2-
Targeted Therapy
8/30/2020 Ibrance (palbociclib)
Chemotherapy
1/14/2021 Carboplatin (Paraplatin), Gemzar (gemcitabine)
