Patients with primary breast cancer can develop distant relapse to the bones, brain, liver and lung. The golden standard to diagnose the lesion and assess its receptor status is a biopsy. However, there are cases in which biopsies cannot be obtained due to the location of the lesion. Do you know how often it is the case that a biopsy cannot be obtained? Thank you!
To my knowledge, no spesific study on the issue you pointed out, exists.
We can however get some insight from biopsy studies:
Bone biopsies seem to be most prone to failure (36%) and 20% of overall biopsies are considered to be insufficient due to various reasons. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015424/)
Complications are associated in 1% of biopsies (https://www.ncbi.nlm.nih.gov/pubmed/24508104/)
About 1% of patients willing to undergo biopsy do not get a biopsy due to safety issues (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046433/)
Overall the percentage of patients from whom (a high quality) biopsy cannot be obtained may be as high as 20%. Only 1% of cases is considered so risky that a biopsy is not attempted.
As you see, to get a definite answer, you need to focus the question. I hope this was of some help. Maybe an interventional radiologist could give a more practical insight.
Antti Roine, thank you very much for your answer, it is very helpful. I know from oncologists that around 20% of all obtained biopsies turn out to be inconclusive (e.g. insufficient). There are, however, cases in which biopsies cannot be obtained at all. So I was trying to quantify that to use it as an input parameter in a cost-effectiveness evaluation model (I am a health economist). Once more, thank you, much appreciated.
Dear Rositsa:
You've already received excellent feedback from Antti above.
What I will do in contrast, is to tackle your shrewd query from a radically difference perspective, namely to significantly question the fundamental reason that second biopsies are often requested, namely what is called RECEPTOR DISSONANCE, based on an internal critical review and appraisal I conducted recently.
THE ISSUE OF RECEPTOR DISCORDANCE: FACT, FICTION, RELEVANCE
The motivation of a second biopsy is often to determine whether there is concordance between the tumor biology of the primary in- breast tumor and a metastatic tumor, and this concern is based on a large - but I will argue again here, methodologically questionable - body of studies that have suggested that the phenomenon of RECEPTOR DISCORDANCE is both substantial (of the claimed order of 20%+) and clinically relevant to treatment decisions, based on putative shifting of the metastatic tumors away from the original ER, PR, and/or HER2 receptor status of the primary.
But is it worthwhile? Most of time, the surprising answer is NO.:
First, the latest (2015) ASCO "Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer" Guidelines [Van Poznak 2015] have concluded that those patients with accessible, newly diagnosed metastases from primary breast cancer should be offered biopsy for confirmation of disease process and testing of ER, PR, and HER2 status. However - and correctly - the ASCO Panel goes on to note that patients should also be informed that if discordances in primary-to-metastatic tumor receptor status are found, we lack ANY robust evidence as to whether outcomes would be materially improved with treatment regimens based on receptor status in the metastatic, or the primary, tumor. The Panel also notes that with discordance of results between primary and metastatic tissues, the panel consensus is to preferentially use the ER, PR, and HER2 status from the metastasis to direct therapy if supported by the clinical scenario and the patient's goals for care.
However, I note that for this last consensus, it too lacks any data to confirm it - it "sounds" right but may be completely wrong (the primary tumor, for instance, does not stay inactive in the on-going metastatic process, and we have strong data to suggest that the primary can continue to "seed" the metastatic tumors).
Second, and more importantly, what is missed by all of the studies on receptor discordance (and the ASCO Panel Guidelines) is:
That there may be "trouble in paradise" began to be suspected when mRNA assays failed to confirm the claimed high incidence of primary-to-metastatic receptor discordance. Since mRNA assays - which have been fully validated recently [Laible 2016] - operate on a more fundamental and reliable level of tumor "reality" than IHC assays and are not subject to their technical limitations, their superiority in detecting true P/M (primary/metastatic) tumor receptor status reversals is above dispute.
So what does an mRNA assay tells? That receptor status shifts are far less frequent when we move beyond the known technical limitations of IHC analysis. For instance, IHC found for ER status a ~23% discordance between primary and metastatic tumor, but in reality, the mRNA assay found only a small ~7% discordance for ER status, and none whatsoever for HER2 status [Wallweiner 2014.]. In addition, and troubling to any clinician, is the fact that IHC claimed to have detected several primary "non-luminal tumors" (mainly ER-negative) turned into metastatic "luminal" tumors with frank hormone receptor expression (ER-positive) , potentially misleading clinicians to treat with endocrine therapy, a mistake given that NO such cases was observed using the mRNA approach [Wallweiner 2015].
CLINICAL RELEVANCE: These findings are disturbing and suggest strong caution in any claimed receptor discordance between the primary tumor and the metastatic tumor, when that is based on IHC, as the far more reliable and validated mRNA assay technique shows that receptor shifting (primary/metastatic) is much more limited in incidence than IHC-based data has been suggesting, with claimed "regaining" of endocrine (ER) status to be treated with considerable suspicion, as too any claim of shift in HER2 status, as mRNA failed to uncover ANY instances of this (in either direction).
If would appear therefore, before any major change in treatment is contemplated due to IHC-based detection of primary/metastatic receptor discordance / shift, that validation of the discordance as true should first be undertaken by mRNA assay.
Otherwise we may be jumping to the tune of IHC "artifacts" (technical limitations) rather than tumor biological reality.
Methodology for this Review
A search of the PUBMED, Cochrane Library / Cochrane Register of Controlled Trials, MEDLINE, EMBASE, AMED (Allied and Complimentary Medicine Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, ISI Web of Science (WoS), BIOSIS, LILACS (Latin American and Caribbean Health Sciences Literature), ASSIA (Applied Social Sciences Index and Abstracts), and SCEH (NHS Evidence Specialist Collection for Ethnicity and Health) was conducted without language or date restrictions, and updated again current as of date of publication, with systematic reviews and meta-analyses extracted separately. Search was expanded in parallel to include just-in-time (JIT) medical feed sources as returned from Terkko (provided by the National Library of Health Sciences - Terkko at the University of Helsinki). Unpublished studies were located via contextual search, and relevant dissertations were located via NTLTD (Networked Digital Library of Theses and Dissertations) and OpenThesis. Sources in languages foreign to this reviewer were translated by language translation software. Gratitude is expressed to the many health professionals who read the manuscript of this review and provided valuable feedback.
REFERENCES
[Laible 2016] Laible M, Schlombs K, Kaiser K, et al. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer. 2016 Jul 7;16:398.
[Van Poznak 2015] Van Poznak C, Somerfield MR, … Harris LN. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.
J Clin Oncol 2015 Aug 20; 33(24):2695-704JC.
[Wallweiner 2014] Wallweiner et al. Concordance/discordance rates of HER2, ER, PR, and Ki67 in matched pair samples of primary (PBC) and metastatic breast cancer (MBC) tissues when comparing IHC with MammaTyper® RT-PCR kit. SABCS 2014. [Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX]
[Wallweiner 2015] Wallweiner et al. Gene and protein expression profiles of HER2, ER, PR, and Ki67 in matched pair samples of primary (PBC) and metastatic breast cancer (MBC) tissues. SABCS 2015. [Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX]
Kind regards
Constantine
Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Cases in which biopsies cannot be obtained at all are rare. However, there are circumstances preventing lesions to be biopsied. The most common cause seems to be insufficient blood coagulation especially in patients with liver failure; followed by insufficient respiratory capacity for lung biopsy in patients with lung diseases. Usually, these conditions do not affect patients with metastatic breast cancer until the terminal state. The only case in which the biopsy was regarded to be too dangerous due to technical reasons in our center within the last 10 years was a lesion located dorsally in the lung. In this case, there was the danger of air embolism. The percentage of cases in which biopsies cannot be obtained at all is difficult to estimate, because these cases are sorted out by their treating physicians, and to my knowledge no statistics are available regarding this point. I agree with an estimation of