ASCO Issues Guidelines on Using Biomarkers to Make Adjuvant Treatment Decisions for Women Diagnosed With Early-Stage Invasive Disease

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The American Society of Clinical Oncology (ASCO) has put out new guidelines on using biomarkers to make decisions about systemic therapies after surgery to treat women diagnosed with early-stage invasive breast cancer.

The guidelines were published online on Feb. 8, 2016 by the Journal of Clinical Oncology. Read “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.”

ASCO is a national organization of oncologists and other cancer care providers. ASCO guidelines give doctors recommendations for treatments and testing that are supported by much credible research and experience.

Biomarkers are certain genetic characteristics in cancer cells that can help predict how the cancer will respond to certain treatments. For example, HER2 status is a biomarker. If a cancer is HER2 positive, it’s very likely that the cancer will respond to anti-HER2 medicines such as Herceptin (chemical name: trastuzumab), Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), Perjeta (chemical name: pertuzumab), or Tykerb (chemical name: lapatinib). Other biomarkers include estrogen-receptor status, progesterone-receptor status, and BRCA1 and BRCA2 status.

Adjuvant treatments are treatments given after breast cancer surgery to lower the risk of the cancer coming back (recurrence).

Systemic treatments are treatments that involve the entire body, not just the area where the cancer was. Chemotherapy, hormonal therapy, and targeted therapies are systemic therapies.

When a person is diagnosed with breast cancer, doctors do a biopsy and run a number of tests on the tissue removed to determine the characteristics of the cancer, including hormone-receptor and HER2 status. This information helps guide treatment decisions.

The new ASCO guidelines offer doctors advice on which biomarkers and tests other than hormone-receptor and HER2 status should be considered when making systemic treatment choices after surgery for women diagnosed with early-stage breast cancer. If the guidelines do not recommend a certain test or biomarker status to guide treatment decisions, it’s because the ASCO experts felt that not enough research had been done to make a recommendation.

The guidelines say:

  • Women diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes may have the Oncotype DX test to help make decisions about whether chemotherapy after surgery offers benefits. The Oncotype DX test should not be used if a woman is diagnosed with HER2-positive disease, triple-negative disease, or if cancer is found in the lymph nodes.
  • Women diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes may have the EndoPredict test to help make decisions about whether chemotherapy after surgery offers benefits. The EndoPredict test should not be used if a woman is diagnosed with HER2-positive disease, triple-negative disease, or if cancer is found in the lymph nodes.
  • Doctors should NOT use the MammaPrint test to make decisions about chemotherapy after surgery for women diagnosed with hormone-receptor-positive, HER2-negative disease. The MammaPrint test also should not be used to make decisions about treatments after surgery for women diagnosed with HER2-positive disease or women diagnosed with triple-negative disease.
  • Women diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes may have the Prosigna Breast Cancer Prognostic Gene Signature Assay test to help make decisions about which treatments after surgery would offer benefits. The Prosigna test should not be used if a woman is diagnosed with HER2-positive disease, triple-negative disease, or if cancer is found in the lymph nodes.
  • Women diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes may have the Breast Cancer Index test to help make decisions about which treatments after surgery would offer benefits. The Breast Cancer Index test should not be used if a woman is diagnosed with HER2-positive disease, triple-negative disease, or if cancer is found in the lymph nodes.
  • Doctors should NOT use the Mammostrat test to make decisions about treatments after surgery for women diagnosed with hormone-receptor-positive, HER2-negative disease. The Mammostrat test also should not be used to make decisions about treatments after surgery for women diagnosed with HER2-positive disease or women diagnosed with triple-negative disease.
  • Doctors should NOT use the immunohistochemistry 4 (IHC4) test to make decisions about treatments after surgery for women diagnosed with hormone-receptor-positive, HER2-negative disease. The IHC4 test also should not be used to make adjuvant systemic treatment decisions for women diagnosed with HER2-positive disease or women diagnosed with triple-negative disease.
  • Women diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes may be tested for urokinase plasminogen activator and plasminogen activator inhibitor type 1 levels to help make decisions about whether treatments after surgery offer benefits. Urokinase plasminogen activator and plasminogen activator inhibitor type 1 levels should not be used to make treatment decisions if a woman is diagnosed with HER2-positive disease or triple-negative disease.

    The urokinase plasminogen activator and its inhibitor are proteins that help breast cancer cells grow and spread. Higher levels of these proteins have been linked to worse prognosis.
  • Doctors should NOT use circulating tumor cell levels to make decisions about treatments after surgery. Circulating tumor cells are cells that break off from a cancer tumor and move into the blood stream.
  • Doctors should NOT use levels of tumor-infiltrating lymphocytes to make decisions about treatments after surgery. Tumor-infiltrating lymphocytes are white blood cells that have left the blood steam and moved into a cancer tumor.
  • Doctors should NOT use Ki-67 protein levels in tumor cells to make decisions about treatments after surgery. The Ki-67 protein is also called the protein encoded by the MKI67 gene. Ki-67 protein levels increase in cells as they prepare to divide. The higher the Ki-67 levels, the more quickly the cells are dividing.
  • If a woman has been diagnosed with hormone-receptor-positive, HER2-negative disease with no cancer in the lymph nodes and has been on hormonal therapy for 5 years with no recurrence, doctors should NOT use the Oncotype DX, EndoPredict, Prosigna, Breast Cancer Index, or IHC4 tests to guide decisions on extending hormonal therapy for 5 more years, for a total of 10 years of hormonal therapy.

The guidelines also make recommendations about which biomarkers have been shown to be helpful when deciding on specific medicines after surgery. While some studies have suggested that certain biomarkers may indicate that a cancer won’t respond to a certain medicine, the ASCO experts felt that more research is needed before they could make a recommendation.

The guidelines say:

  • A woman’s CYP2D6 status should not influence the type of hormonal therapy recommended for her.

    The body uses an enzyme called CYP2D6 to convert tamoxifen into its active form. The CYP2D6 enzyme is made by the CYP2D6 gene. About 10% of people have a CYP2D6 genotype (a classification of the CYP2D6 gene) that doesn’t function as it should and so doesn’t make enough of the CYP2D6 enzyme. Some smaller studies found that people with certain CYP2D6 genotypes might not get all the benefits of tamoxifen. After these smaller studies were published, some doctors and women began to ask for CYP2D6 genetic testing. But several large studies have found no link between CYP2D6 genotypes and the effectiveness of tamoxifen.
  • Doctors should not use Ki-67 protein levels in tumor cells to make recommendations about the type of hormonal therapy prescribed after surgery. Some small studies have suggested that cancer cells with high levels of Ki-67 don’t respond well to aromatase inhibitors.
  • Doctors should not use levels of microtubule-associated protein Tau in cancer cells to make decisions about which chemotherapy regimen should be used after surgery. Some studies have suggested that high levels of microtubule-associated protein Tau in breast cancer cells may mean the cancer is resistant to taxane chemotherapy.
  • Doctors should not recommend chemotherapy medicines based on a cancer’s TOP2A and HER2 status. Some research suggests that cancers that are HER2-positive and TOP2A-positive respond better to chemotherapy regimens that include an anthracycline such as Adriamycin (chemical name: doxorubicin).
  • Doctors should not use a cancer’s PTEN status to make recommendations about targeted therapies for HER2-positive breast cancer. Some research suggests that PTEN-negative breast cancers may be resistant to Herceptin. The PTEN protein suppresses tumor growth.

If you’ve been diagnosed with early-stage breast cancer, you and your doctor will consider a number of factors when deciding on treatments. In addition to some of the biomarkers listed in the ASCO guidelines, you’ll also consider:

  • the results of any genetic testing you’ve had
  • any treatments you’ve already had
  • the type of surgery you had
  • your general health
  • your personal preferences

For more information, visit the Breastcancer.org Your Diagnosis pages.



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