No announcement yet.

Can Biopsies of Liver Metastases Improve Treatment Choice?

  • Filter
  • Time
  • Show
Clear All
new posts

    Can Biopsies of Liver Metastases Improve Treatment Choice?

    Analyses of the levels of estrogen receptor (ER), progesterone(Drug information on progesterone) receptor (PgR), and human epidermal growth factor receptor 2 (HER2) are standard practice following an initial breast cancer diagnosis. This characterization is important to subtype the cancer and determines the choice of therapy.

    It is currently not routine practice to re-biopsy metastatic tissue to re-evaluate treatment options based on tumor characteristics. This is despite the fact that, upon progression to metastasis, cancers can evolve, resulting in changes in mutations and expression levels of specific markers. Biological changes between the primary and secondary tumors can occur, but have not been systematically studied.

    Researchers at the University of Milan sought to assess the clinical relevance of biopsying primary breast cancers and secondary metastatic liver lesions to evaluate the occurrence of important markers. They asked whether changes occur frequently enough to warrant the biopsy of secondary cancers, which could potentially improve treatment options. The results of the 1250-patient retrospective study are published ahead of print in the Annals of Oncology (doi:10.1093/annonc/mdq751).

    The study found discordance rates for ER, PgR, and HER2 between primary tumor and liver metastases of 14.5%, 48.6%, and 13.9% (24 of 172 patients), respectively. 5.9% of patients changed from a negative to a positive HER2 status. A discordance of status of any of the three biomarkers led to change in treatments for 12.1% (31 of 255) of patients.

    Interestingly, the study observed a concomitant decrease in ER and PgR expression along with liver metastases turning HER2-positive. The authors hypothesize that there is potential cross-talk between pathways that suggests that endocrine resistance is being mediated by HER2 up-regulation within the tumor.

    Although this was a retrospective, non-blinded study, it was strengthened by being a single-institution study. Thus, all pathology, biopsies, and assays carried out in the same laboratory thereby minimizing inter-laboratory variability.

    Improving and optimizing the care of patients with metastatic breast cancer relies on a thorough understanding of the biology of the disease and how it may differ between the primary and the metastatic disease setting.

    The major reasons that biopsies of metastatic breast cancer are not part of standard care are the lack of previous evidence of utility, reluctance of allowing an invasive, surgical procedure for an advanced-disease patient, and potential harm of a false-negative result. When safe and relatively easy to carry out, a biopsy of metastatic disease has the potential to impact treatment of choice. However, more studies are necessary before metastatic breast cancer biopsies become standard of care.

    Anna Azvolinsky, PhD
    Gregory D. Pawelski

    Resection and Local Ablation of Breast Cancer Liver Metastases

    Liver Resection and Local Ablation of Breast Cancer Liver Metastases—A Systematic Review

    M Bergenfeldt, BV Jensen, B Skjoldbye, D Nielsen



    To analyze surgical treatment of breast cancer liver metastases (BCLM) regarding selection criteria, outcome and prognostic parameters.


    We searched Embase and Medline for all studies published 1999–2010.


    Resection was associated with a median survival (MOS) of 20–67 months and 5-year survival of 21–61%. Local ablation also had a favorable outcome; MOS was 30–60 months and 5-year survival 27–41%. Regarding selection, no specific limits regarding the number and size of BCLM can be given. Features of the primary breast cancer (BC) were not significant for the prognosis. Microscopically radical (R0) resection is a positive prognostic factor, while the effects of disease interval, hormone receptor status and response to preoperative chemotherapy were divergent. The presence of extrahepatic disease (EHD) had a negative effect on survival in some studies, but failed to have so in other studies.


    Surgical therapy may benefit a subset of patients with BCLM. Resection may be indicated, if an RO-resection can be done with a low risk of mortality. Liver resection in the presence of extrahepatic disease remains controversial, while patients with BCLM and bone metastases could possibly be managed differently than other EHD.

    Source: Eur J Surg Oncol. 2011 Jul 1;37(7):549-557
    Gregory D. Pawelski


      Can chemotherapy ever be bad, in cases where it apparently works?

      Can chemotherapy ever be bad, in cases where it apparently works? The mutagenic effects (changes in form) of chemotherapy on the genetically-unstable tumor, driving the tumor into a state of more aggressive behavior.

      You might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more agressive fashion. Like when chemotherapy on an ER+ cancer brings about a remission, but in the process also causes any remaining cancer to become ER-.

      It seems entirely reasonable that effective, although mutagenic therapy would be preferred over ineffective, mutagenic therapy. Chemotherapy not only causes mutations, which might make a given cancer more agressive, but it can cause second malignancies as well.

      Chemotherapy has many adverse effects which can affect any system of the body. Some may not appear until after treatment is completed. A major obstacle in controlling cancer growth and metastasis in patients is the widespread inappropriate use of anti-cancer drugs.

      Because tumors originate from a wide variety of genetic backgrounds, most cancer cases have become unsuited to the use of "standardized" chemotherapy. Since no single drug or combination has been found to be optimal for cancers of all origins, developing a good and clinically practical "drug selection" system is no less important than the discovery of new drugs.

      All laboratory tools should be at the disposal of the oncologist, for the patient. The functional profiling platform doesn't change cancer biology, it helps to reveal biology. It lowers the probability that certain drugs will work. It raises the probability that others will work (on the individual, no populations).

      Cancer patients would certainly have a better chance of success had their cancer been "chemo-sensitive" rather than "chemo-resistant," where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

      Improving cancer patient treatment through proper drug selection can enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different from patient to patient, from primary to metastasis, the response to given drugs is very different, and cancer cells do no always develop into an active secondary tumor when they have spread to a new site. Sometimes a metastasis is just another primary.

      "It is currently not routine practice to re-biopsy metastatic tissue to re-evaluate treatment options based on tumor characteristics." More studies are necessary before metastatic breast cancer biopsies become standard of care? Give her another grant to keep her lab going? And you wonder why cancer patients are "chasing mets."
      Gregory D. Pawelski


        Chasing Mets (Metastasis)

        On most cancer discussion boards, one of the most common themes is that of "chasing mets" (metatasis). Cancer patients are chasing mets because of the wrong type of chemotherapeutic regimens for their type of cancer histology. But why do patients with histologically similar tumors respond differently to so-called "standard" drug treatments? That is one of the main problems associated with chemotherapy. Patient tumors with the same histology do not necessarily respond identically to the same agent or dose schedule of multiple agents.

        Medical oncologists select a drug and must wait to see whether it is effective on a particular patient. Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual. And when patients develop metastatic cancer, it is often difficult to select an effective treatment because the tumor develops resistance to many drugs. For many cancers, especially after a relapse, more than one standard treatment exists.

        A chemoresponse assay is a diagnostic test (not a treatment) to help measure the "efficacy" of cancer drugs. They cannot make the cancer drugs do better, it can only measure the "best" probability of successful drugs. This is in stark contrast to "standard" or "empiric" therapy (also called physician's choice therapy), in which chemotherapy for a specific patient is based on results from prior clinical studies.

        Laboratory screening of samples from a patient's tumor (if available) can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents. It can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free and overall survival.

        It would be highly desirable to know what drugs are effective against particular cancer cells before cytotoxic agents are systemcially administered into the body. Chemoresponse assays are clinically validated drug tests on living (fresh) specimens of cancer cells to determine the optimal combination of chemotherapy drugs. These assays are specifically tailored for each individual patient based on tumor tissue profiling, with no economic ties to outside healthcare organizations, and recommendations are made without financial or scientific prejudice.

        Recommendations are designed scientifically for each individual patient. Various assays are performed on a tumor sample to measure drug activity (sensitivity and resistance). This will determine not only what drug or combinations of drugs will not effectively work, but which will be most effective for an "individual's" cancer. Then a treatment recommendation is developed through what is known as "assay-directed" therapy.

        Second, third, even fourth line therapies (why?)

        I often read on the boards about oncologists telling patients "if this drug doesn't work, we'll try this drug." And "if that drug doesn't work, we'll try this drug." In patients who have failed two, three or even four chemo drugs, why not give them the "right" drug or combinations the first time around?

        In academic centers, patients are entered into clinical trials of "square peg in a round hole" therapy. This encourages the patient to receive second, third, and fourth line chemotherapy, regardless of the likelihood of meaningful benefit. The therapies are equivalent on a "population" basis, but not on an "individual" basis.

        They continue to try and mate a notoriously heterogeneous disease into "one-size-fits-all" treatments. They predominately devote their clinical trial resources into trying to identify the best treatment for the "average" patient, in the face of evidence that this approach is non-productive.

        According to NCI's official cancer information website on "state of the art" chemotherapy in recurrent or metastatic cancer, no data support the superiority of any particular regimen. There is no proven "standard" first line therapy which has been shown to be superior to the many other choices which exist.

        The same situation exists in the setting of second, third, and fourth line therapy. Proven by the large number of patients who have progressive disease on first line therapy but who have good responses to second or third line therapy.

        So it would appear that published reports of clinical trials provide precious little in the way of guidance. These patients patients should have received the "correct" treatment in the first line setting. This can be accomplished by individualizing cancer treatment based on testing the cancer biology.

        Gynecol. Oncol. 88 [1], 2003
        Am J Obstet Gynecol. 2003 Nov;189(5):1301-7
        Eur J Clin Invest, Volume 37(suppl. 1):60, April 2007
        J Clin Onc. 2008; 26: May 20 supplement. Abstract #16522
        Gregory D. Pawelski