A saliva test for triple negative breast cancer?

[NNadir]

While working on a project for my job, I stumbled upon this paper which is not related to the syndrome I'm currently studying: Kuldeep Giri, Sudipa Maity, Kiran Ambatipudi, Targeted proteomics using parallel reaction monitoring confirms salivary proteins indicative of metastatic triple-negative breast cancer, Journal of Proteomics, Volume 267, 2022, 104701.

Triple negative is the really bad form of breast cancer; we're making progress, but by no means are we "there yet."

We do have very powerful analytical tools, and the degree of sophistication I've seen in just the last five years in mass spectrometry just blow my mind; I can hardly keep up.

Unfortunately I can't spend much time on this paper, but here's a few excerpts:

Breast cancer is a common malignancy among women, and its incidence rate is increasing worldwide, irrespective of the country's economic status. In 2020, approximately 2.3 million women were diagnosed with breast cancer, of which 685,000 deaths were reported globally [1]. However, in the past three decades, the mortality rate due to breast cancer has consistently declined in countries with the implementation of screening and local management of early breast cancer, advanced modes of treatment (e.g., surgical removal, therapy, and medication), including the emergence of the adjuvant systemic therapies [2]...

...Breast cancer is a biologically and molecularly heterogeneous disease originating from the breast [3]. Based on the gene expression pattern of four well-established biomarkers, such as estrogen receptor alpha (ER? ), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation-associated nuclear antigen (Ki-67), breast cancer tumours have been categorized into five distinct subtypes, i.e., Luminal A and B, Triple-negative, Normal-like, and Her-2 enriched breast cancer [4]. This molecular/clinical subtype classification is often used to decide the appropriate therapeutic strategies and set the critical reference for prognosis [5].

Among the different breast cancer subtypes, triple-negative breast cancer (TNBC) is a heterogeneous set of cancer characterized by no ER/PR and Her-2 protein expression. It is the most aggressive subtype and grows faster than other subtypes. It has a poor prognosis with no effective targeted therapy due to the absence of any receptor status [6,7]. TNBCs mainly affects younger women (less than 50 years of age) with a higher frequency of p53 mutations and at a higher risk of death by distant recurrence, especially during the first 3–5 years of follow-up. Importantly, TNBC metastasizes predominantly to visceral organs than bones, including a higher incidence of cerebral metastases and a higher rate of local relapse in patients than any other subtypes...

After some other stuff, the authors discuss mass spectrometry and breast cancer and give their research goal:

...Mass-spectrometry (MS) has found its application in cells, tissue, and biofluids to identify and characterize potential biomarkers. For instance, untargeted proteomics has been employed to investigate potential markers of TNBC in breast cancer tissue [10,11] or biofluids such as serum and plasma [12,13]. Few studies have also reported validated markers for TNBC using MS-based targeted quantitation in blood samples [14] and breast cancer tissue [[15], [16], [17]]. However, only limited information is available on salivary proteomics [[18], [19], [20]]. Their validation could reflect saliva as an adequately complex fluid investigating potential markers in TNBC.

Due to the propensity of ease of collection and enrichment of low abundant proteins in saliva, we used an MS-based label-free untargeted approach for relative quantitation coupled with absolute targeted quantitation using parallel reaction monitoring (PRM)-based assay to investigate potential salivary protein markers associated with TNBC and its metastasis...

A graphic from the paper:



There's a lot of cool stuff in this paper that I regrettably won't have time to share, but it's promising, but needs confirmation:

...To facilitate the verification and potential translation of these proteins and peptides for clinical application, they were assessed for their diagnostic performance to determine the sensitivity, specificity, and positive/negative predictive values. To this end, we observed that GLST and VYAL with an AUC of 0.84 performed better than the other peptides as individual markers. However, compared to one protein's performance as an individual marker, the five-signature panel with salivary GLST, VYAL, MINL, GPYP, and IPPP achieved better performance in differentiating aggressive TNBC and HS with sensitivity (80%) and specificity (95%) (AUCs of 0.89). Although the machine learning approach has been applied to a relatively smaller cohort of patients, it shows promising generalizability, prompting us to target these groups of peptides in a large cohort of TNBC patients to validate in saliva.

Our study is designed in the context of potential marker discovery in non-invasive bio-fluid saliva from TNBC patients utilizing targeted proteomic assays. While our developed assays are subsequently evaluated across multiple independent cohorts, substantial work is still required by validating these proteins in larger independent patient cohorts, preferably in longitudinally collected samples and additional assay optimizations. Here, we provide the first work utilizing PRM-MS to systematically identify these novel salivary proteins as potential markers to distinguish and indicate TNBC progression in a medium-sized cohort...

It's promising, I think, a lead toward large scale simple screening.

Have a nice day tomorrow.

[elleng]

1. Thanks for your work.

[Deuxcents]

2. Very interesting, for sure

I have a dear friend who just completed 33 radiation treatments for cancer of the saliva glands. I’m wondering if tests need to be done on that first before testing for breast cancers. Thankfully, medicine n science are progressing on this horrible cancer..and all cancers, for that matter.

[NCjack]

3. Until this test is proven, your best defense is still early detection in a breast

of a new abnormal feature by self-examination. Everytime you shower or bath.

You cannot depend on your partner alone for detection. The new abnormality may be a new lump or a new depression. That is right -- a depression!

[NNadir]

5. This is decidedly true. This test is only in a very preliminary phase...

...in this case, as the authors make clear.

Given the expected false discovery rate that one can expect, it should be considered only for screening purposes and be subject to confirmatory testing.

Notably, it only covers, even if subject ultimately to regulatory approval, a stage to which it will advance if the development pans out, triple negative, and not the other types of breast cancer.

It should prove useful for preparing surgeons and pathologists for what they may see on biopsy and tumor morphology.

This test depends on access, at least for now, on high resolution mass spectrometry, expensive instruments, but almost certainly can be moved to less expensive and more available (in CLIA labs) triple quad mass specs if it is fully validated.

It's a lead, not a result. For now everyone should do what is confirmed to work best, including self examination.

[Wounded Bear]

4. Sounds like it could be a game changer...

any non-invasive test for cancer should be investigated thoroughly.