Lumpie

I asked my MDACC team if I was in the match trial. They said yes, but never once contacted me about anything potential. I am learning that you have to be proactive to get on a trial and that sometimes it's all about timing.

My local MO read that erubulin paper. He said I can keep it in my bucket but he prefers me to try a platinum drug combo next because of the Neuroendocrine part.

Thanks for keeping us all informed!

Dee

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."

Bev, 2006??? Are you kidding me? Science should be investigating you in and out - you are one of a kind!:) Best of luck for Friday again... Saulius

Lynn,

Wow. I hadn't focused before on the fact that you were 26 years out when you had recurrence. That's a wild story. Saulius noted that scientists should follow me, now 16 years out from that first metastasis; likewise, they should be studying you. Your story and mine simply highlight how much science does not understand the mechanism of metastasis, especially metastasis after a long period of dormancy.

Thank you Lumpie. I do believe that giving cancer cells a "vacation time" makes them mutate and re-organize to metastasis. Sneaky disease.

AlabamaDee, thanks for posting this! More motivation for me to stick to my low carb eating plan! That was the only way I could lose any significant amount of weight post-menopause.

Some good info coming out of virtual SABCS

You are correct it isn't the same Moth, I would say it's more flexible.

Here is a handy chart-

Gylcemic Chart

yes low glycemic and KETO are different. I just lived KETO for a year and know it worked for me. My A1c and glucose are fine and I have always been an overweight person. Not doing anything drastic until after Xmas.

Dee, do you have a link to that article (if it was an article)? Thanks!

Study can orient use of melatonin in the treatment of breast cancer

A Brazilian study published in the Journal of Pineal Research describes a group of genes potentially regulated by the hormone melatonin in some types of cancer, especially breast cancer. According to the authors, the results can be used to guide future personalized therapies for the disease...

As a result, they were able to understand how melatonin works in several cellular signaling pathways. "These genes targeted by melatonin relate to important biological processes in cancer, such as cell cycle regulation, cell death, and cell migration and senescence," he explained. "Melatonin appears to act more strongly on breast, oral, and stomach cancer...

According to Chuffa, genes regulated by melatonin in breast cancer are potential targets for the treatment of the disease. "Melatonin is a multitasking molecule and acts on various cellular substrates, so we're now taking the study deeper to find out how the hormone influences microRNA expression and hence the regulation of the cellular mechanisms identified," he said.

https://www.eurekalert.org/pub_releases/2020-12/fd...

Wait, I just realized-- Dee, your doctor is Dr. Hamilton? She seems to be pretty awesome. I follow her on twitter.

There isn't an article to link the info was from a presentation at the San Antonio BC Symposium. There might be info here: SABCS News Or you can find some commentary from doctors and patients re. on twitter if you search the hastag #SABCS20

I'm sure more info will be coming out. The takeaway is really that a healthy diet is a low glycemic diet so the more you can follow that the better your overall health will be long term.

Re: whether common cholesterol drugs might improve the reach of immunotherapy--

https://www.cancer.gov/news-events/cancer-currents...