Hormone and HER2 Receptor Status Can Change When Breast Tumo

[schoolteacher]

good to hear. Thank you. I hope you are holding up ok also? Day 3-7 are often when the chemo kicks in. Hopefully it will not be too unkind to mum. Make sure she tells her onc about any problems as meds can help enormously. Take care hun.

[neptune]

Thanks school teacher. She's ok! She had her first chemo on Monday, and the nurse had a lot of trouble getting flashback from her port so it took ages!! But she's ok, just tired. I think it will take a bit longer for the "real" side effects to hit?

[schoolteacher]

How is mum going Neptune? I have been thinking of her a lot

[neptune]

That's very interesting. My mums histopathology changed in 2 weeks from er/pr negative to er/pr positive!

[schoolteacher]

Interesting Thanks nav

[yowyow]

We have discussed this before - I think its so important to demand
any progression to be tested

Hormone and HER2 Receptor Status Can Change When Breast Tumors Progress
Elsevier Global Medical News. 2010 Jul 1, P Wendling


CHICAGO (EGMN) - The need to reassess the biology of breast cancer after it progresses was driven home in three studies described as the largest to date to tackle the issue of hormone receptor discordance.

Smaller, mostly retrospective studies using varying methodology to evaluate receptor status have reported discordance between the primary tumor and progressive disease ranging from 18% to 55%. Some have suggested that discordance may be associated with poorer survival due in part to inappropriate choice of targeted therapies.

"Despite this, management of metastatic disease has not changed, and is usually still based on primary tumor characteristics," said Dr. Andrea L. Richardson, from the Dana-Farber Cancer Institute in Boston, at the annual meeting of the American Society of Clinical Oncology, where she discussed the three new studies - all of which produced relatively consistent rates of discordance.

Discordance rate was 39% overall

The first abstract was a pooled analysis involving 271 women from the recent multicenter BRITS study in the United Kingdom and the single-center DESTINY study in Canada, which prospectively evaluated the receptor status of primary and recurrent disease using immunohistochemistry and fluorescent in situ hybridization (FISH). All told, 132 women had local-regional recurrence and 139 had distant recurrence.

The discordance rate was 39% overall, with differences of 13% for estrogen receptor status, 34% for progesterone, and 5% for HER2, reported Eitan Amir, MB, ChB, from Princess Margaret Hospital in Toronto.

The discordance rate in triple-negative tumors was very low at 7% vs. 45% in non-triple negative tumors - a finding that Dr. Richardson said needs further study and validation.

The duration between primary and recurrent disease, which ranged from 0 to 332 months (median 79 months), does not appear to affect receptor discordance (P = .360), Dr. Amir said.

Biopsy results did alter management in 41 or 15% of women, which translated into 1 change in systemic therapy for every 6.6 biopsies (P less than .0001), he said. The most common reasons for change in management were changes in HER2 status, gain of hormone receptor status, and identification of benign disease or second malignancy.

The study defined discordance as change from positive or negative or vice versa; quantitative change in receptor expression was not defined as discordance. "Biopsy should be considered to confirm disease recurrence in breast cancer," the authors concluded.

Almost 1 in 3 patients changed status

Nearly every third patient with breast cancer had changes in hormone receptor status during tumor progression, according to an analysis involving 486 women whose information on hormone receptor status was retrospectively collected from pathology reports.

Estrogen receptor (ER) status changed in 27% from positive in the primary tumor to negative in relapse and 8% changed from negative to positive, reported Dr. Eva Karlsson from the oncology-pathology department at the Karolinska Institute in Stockholm.

Progesterone receptor (PR) status changed from positive in the primary tumor to negative in relapse in 38% of 456 evaluable patients and changed from negative to positive in 5%.

Univariate analysis revealed almost a twofold increased risk of death in patients losing ER-positive status during tumor progression, compared with stable ER-positive patients (adjusted hazard ratio 1.91).

The data together with multiple small and retrospective data underlies the need for practice change, Dr. Karlsson said. "Therapy management of metastatic disease is suboptimal when only based on primary tumor characteristics," she said.

Treatment changed in 12% of patients

Researchers at the European Institute of Oncology in Milan used pathology and medical reports to retrospectively evaluate receptor status in 255 consecutive women with breast cancer who developed liver metastases. The women underwent liver biopsies at the institute from August 1999 to March 2009, after a median of 3.4 years from their primary diagnosis.

Changes in ER status were observed in 37 or 14.5% of 255 patients (P = .001), with 15 of 58 ER-negative primary tumors turning into ER-positive liver metastases and 22 of 197 ER-positive primary tumors turning into ER-negative metastases, Dr. Marzia Locatelli and her colleagues reported.

Analyses of PR status showed that 124 changed status for an overall discordance rate of 48.6% (P less than .0001). Among 91 negative primary tumors, 18 converted to positive liver metastases while 106 of 164 positive primary tumors became negative.

While 83 patients were missing HER2/neu status in their primary tumor or liver biopsy, 24 (14%) of 172 of patients had discordance (P less than .001). Again discordance was more common among positive primary tumors with 17 of 54 becoming negative, while 7 of 118 negative primary tumors became positive.

Overall, discordance between primary tumors and liver metastases led to changes in endocrine therapy or immunotherapy for 12% (31 of 255) patients, the investigators reported.

"In the era of continuing biological and therapeutic advances, should we continue to use a historical pathological snapshot of the primary tumor or should we reassess the biology of metastatic disease?" Dr. Locatelli asked.

She suggested that when safe and easy to perform, a biopsy of the metastatic lesion should be considered in all patients, particularly when there is a long interval from the first diagnosis, since it is likely to affect treatment choice.

Measurement error and biology

Dr. Richardson and several of the researchers cited possible reasons for the discordance including a delay in fixation of the tumor sample, fluctuations around the cutoffs used by different labs for defining ER positive vs. ER negative, and heterogeneity within tumors.

Receptor studies are generally performed only on a single block of the primary breast tumor or often on a limited core biopsy of the tumor. Failure to detect a significant subpopulation with different receptor expression within a large primary tumor may explain discordances, Dr. Richardson said. This led her to question whether there is an association between tumor size and likelihood of discordance, and whether clinicians should evaluate more areas of the primary tumor.

Assuming there is heterogeneity within a primary tumor, treatment might select out the subpopulation that does not express the target. This could explain the loss of ER status in recurrences after endocrine therapy, loss of HER2 after HER2-targeted therapy or even perhaps gain of ER after cytotoxic chemotherapy, she said.

The relevance of discordance

Ultimately, the reason for discordance may not be important, Dr. Richardson said. A substantial portion of patients - 12% to 15% - will have a change in therapy on the basis of different receptor expression in the recurrent tumor as compared to the primary tumor. Dr. Karlsson's data also suggest that patient survival is more related to receptor expression in the recurrence than receptor expression in the primary.

"Therapy is determined by receptor status and we need to treat the tumor that is present now, not the tumor that used to be there years before," Dr. Richardson said.

Disclosures: Dr. Amir and colleagues report relationships with AstraZeneca Pharmaceuticals, F. Hoffmann-La Roche Ltd., and Novartis. Dr. Karlsson and colleague report relationships with 10 pharmaceutical companies. Dr. Locatelli and colleagues report no relevant conflicts. Dr. Richardson disclosed no conflicts.


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