Pathology questions

marycal

I finally got my pathology report back today from a core needle biopsy. We've known for weeks that it's IDC, but had to wait for the details. I am getting some conflicting info online about ki67. Mine is 5-10%, and my surgeon said this was very low. Searching the internet, I'm seeing that could be considered intermediate. I'm also not sure what relevance the % for the hormone receptors have. I'm ER+ 90% and PR+ 20%. Can anyone help me decipher? Thank you.

cive

You are luminal A - which is very good.  er/pr+ means that the relative percentage of receptors for your breast cancer require estrogen and progesterone to grow, while they do not have what is known as her2 which is fairly aggressive.

BarredOwl

Please confirm the above information regarding Luminal A "subtype" with your Medical Oncologist.

Regarding subtype, I note that while some studies have used IHC markers, such as ER, PR, HER2 and Ki-67, as surrogates or substitutes to assign subtype (e.g., Luminal-A, Luminal-B, HER2-type, Basal-type), "intrinsic subtypes" were originally defined by Perou in 2000 using a very different technology.

Today, different multi-parameter gene expression profiling tests (e.g., BluePrint, PAM50) use different gene sets to approximate the "intrinsic subtypes" originally defined by Perou in 2000 (using a different methodology). See for example:

Krijgsman (2010): "A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response"

ResearchGate free PDF: https://www.researchgate.net/publication/51545570_A_diagnostic_gene_profile_for_molecular_subtyping_of_breat_cancer_associated_with_treatment_response

(X-out and scroll down to access full pdf)

As for use of IHC to determine subtype, the 2015 St. Gallen panel remarked:

"As in previous St Gallen meetings, the Panel was of the strong opinion that the distinction between strongly endocrine responsive, low proliferation, good prognosis 'luminal A-like' and less endocrine responsive, higher proliferation, poorer prognosis 'luminal B-like' (HER2-negative) tumors could be derived from IHC tests for ER, PgR and Ki-67, though the use of Ki-67 required knowledge of local laboratory values. (The Panel used these terms as a shorthand in classifying hormone receptor-positive disease into luminal A-like and luminal B-like subsets, though it recognized that IHC tests do not accurately measure true intrinsic subtypes.) The corollary was that a clear majority of the Panel did not believe that multiparameter molecular markers were required for this distinction. A majority of the Panel was prepared to accept a threshold value of Ki-67 within the range of 20%–29% to distinguish 'luminal B-like' disease, though about one-fifth of the Panel felt that Ki-67 should not be used at all for this distinction. Only a quarter of the Panel believed that subtype determination could be replaced by risk scores derived from multiparameter molecular markers."

Not surprisingly, when compared head to head, the various subtyping tests are not fully concordant with each other. Thus, for example, it would seem more accurate to say "the tumor was classified as Luminal-type A by BluePrint/MammaPrint" than it would be to say "the tumor is Luminal A". The same would apply to assignment of subtype made using histopathological markers.

BarredOwl

BarredOwl

Hi marycal:

Ki-67 is a protein that is a marker of cell proliferation or cell growth (a higher percentage suggests more dividing tumor cells).

In general, rapidly dividing cells may be more responsive to chemotherapy. The 2015 St. Gallen panel commented:

"There can be little doubt that Ki-67 scores carry robust prognostic information [24], and that high values predict the benefit of addition of cytotoxic chemotherapy [25], but definition of a single useful cut point has proved elusive both because Ki-67 displays a continuous distribution [26], and as a result of analytic and preanalytic barriers to standardized assessment [27]."

In other words, despite the results of studies which report some prognostic and predictive value, there are technical issues with determination of Ki-67 percentages by standard IHC methods, including interobserver variability (different results when different people perform the test on the same sample) and lack of reproducibility across laboratories, as explained in detail here:

Polley (2013): "An International Ki67 Reproducibility Study"

http://jnci.oxfordjournals.org/content/105/24/1897.full

(Free PDF available via link)

Also, different studies use different values as cut points or cut-offs between what is considered "low" or "high" Ki-67.

All of this makes it difficult to rely on the results of clinical studies in which Ki-67 was determined in other labs and to interpret the clinical significance of a Ki-67 test result based on such studies. Accordingly, some institutions no longer perform Ki-67 testing (at this time), and clinical consensus guidelines (e.g., from ASCO) do not generally support the broad use of Ki-67 protein (determined by standard IHC) to guide adjuvant chemotherapy decisions.

Please ask your medical oncologist for his views on the significance of your Ki-67 result.

BarredOwl