**Trastuzumab - Trastuzumab Biologics**

Trastuzumab is a monoclonal antibody, one of a group of drugs designed to
attack specific cancer cells. Trastuzumab's targets are cancer cells that
overexpress an oncogene called HER2 or HER2/neu, which occurs in high numbers
in about 25 to 30 percent of breast cancers. According to the National
Comprehensive Cancer Network (NCCN), breast cancers can be categorized as
being HER2 positive or HER2 negative. HER2-positive breast cancer is faster
growing and considered more aggressive. Studies indicate that the drug
trastuzumab (Herceptin) is effective in treatment of HER2-positive early stage
breast cancer and HER2-positive metastatic breast cancer. Trastuzumab is not
effective in the treatment of HER2-negative breast cancers.

There are two methods of testing for HER2 tumor status in women with breast
cancer: immunohistochemistry (IHC) and fluorescence in situ hybridization
(FISH). HER2 test results are interpreted as follows:

  * HER2 positive status is IHC 3+ or FISH positive
  * HER2 negative status is IHC 0, 1+ or FISH negative
  * A borderline IHC result of 2+ should be followed by performing a FISH test.
  * A borderline FISH result of an average HER2 gene/chromosome 17 ratio of 1.8 to 2.2 (or an average of greater than 4 to less than 6 HER2 gene copies/cell) should be followed by one of the following: 
    * Counting additional cells in the tissue sample
    * Retesting with FISH
    * Performing an IHC test

Results from both tests are used in the clinical setting, and the results of
the tests influence treatment choices for women with breast cancer. The
pathology laboratory where the HER2 testing is done should be accredited to
perform such testing. It should have quality control procedures in place to
ensure that the test is done correctly, and a quality assurance plan to
validate (i.e., determine the accuracy of) the HER2 test results.

**Covered Indications**

**Trastuzumab - Trastuzumab Biologics**

Trastuzumab and its biologics are covered for Food and Drug Administration
(FDA) approved labeled indications. Please see the FDA drug label for the FDA
approved indications and dosages. This can be accessed at
<https://labels.fda.gov/>.

**Trastuzumab and its biologics will be considered medically necessary when
provided for its FDA approved uses, as well as for the treatment of any of the
following off-labeled indications:**

For metastatic and non-metastatic breast cancer, trastuzumab and its biologics
may be considered medically reasonable and necessary when incorporated into
the adjuvant therapy in the following recommended uses by the NCCN Drugs and
Biologics Compendium:

  1. Preoperative chemotherapy in combination with paclitaxel followed by FEC/CEF (fluorouracil, epirubicin, and cyclophosphamide) regimen with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive stage IIA, IIB, or T3, N1, M0 disease who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size or for patients with locally advanced disease (stage IIIA, IIIB, or IIIC). 
  2. Adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive, stage I, IIA, IIB, or T3, N1, M0 disease (ductal, lobular, mixed, or metaplastic histologies) that is node-positive, node-negative with tumor 0.5 cm or greater in hormone receptor-negative patients, or node-negative with tumor 0.6 to 1 cm, grade 2 or 3, or with unfavorable features or tumor greater than 1 cm in hormone receptor-positive patients, or for patients with locally advanced disease (stages IIIA, IIIB, or IIIC). 
    * concurrently with paclitaxel following AC (doxorubicin and cyclophosphamide) regimen as preferred regimen 
    * in TCH (docetaxel, carboplatin, and trastuzumab) regimen as preferred regimen 
    * in combination with docetaxel followed by FEC/CEF (fluorouracil, epirubicin, and cyclophosphamide) regimen 
    * following chemotherapy 
    * in combination with docetaxel following AC regimen 
  3. Used in combination with aromatase inhibition for the treatment of recurrent or stage IV estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive disease in postmenopausal women* who have received no prior endocrine therapy within one year. 

*Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis.

  4. Preferred regimen for patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer that is hormone receptor-negative or hormone receptor-positive and endocrine refractory and not characterized by bone or soft tissue involvement only or asymptomatic visceral disease as: 
    * first-line chemotherapy in combination with docetaxel, vinorelbine, or capecitabine or with paclitaxel with or without carboplatin 
    * treatment for trastuzumab-exposed HER2-positive disease in combination with lapatinib without cytotoxic therapy, with docetaxel, vinorelbine, or capecitabine, or with paclitaxel with or without carboplatin

The timing of therapy combination with other agents or regimen, dosage, and
duration of therapy should be based on NCCN guidelines and the package insert.

**Limitations**

For limitations of use of trastuzumab and its biologics, please see the FDA
drug label. This can be accessed at: <https://labels.fda.gov/>

As published in the CMS IOM Publication 100-08, _Medicare Program Integrity
Manual_ , Chapter 13, Section 13.5.4, an item or service may be covered by a
contractor LCD if it is reasonable and necessary under the Social Security Act
Section 1862 (a)(1)(A). Contractors shall determine and describe the
circumstances under which the item or service is considered reasonable and
necessary.