Trastuzumab Recommended for HER2 Positive, Invasive Lobular Breast Cancer

Breast Cancer News
June 19, 2013
Nicole Katze, MA, Editor and Manager, Content Development

Herceptin equally benefits early-stage invasive and ductal HER2 positive disease, study shows

Women diagnosed with early-stage breast cancer that begins in the lobules of the breast gain just as much benefit from treatment with trastuzumab (Herceptin) as women with early-stage cancer that starts in the ducts of the breast, researchers found. Their study used data from the Herceptin Adjuvant (HERA) trial.

Breast cancers that start in the lobules, the glands that produce breast milk, and travel through the breast wall are known as invasive lobular carcinoma, or ILC. Those that start in the ducts, the passages that carry milk from the lobule to the nipple, and travel through the breast wall are known as invasive ductal carcinoma, or IDC. ILC is a rarer form of the disease, while IDC is the most common type of breast cancer diagnosed.


HERA, the Herceptin Adjuvant Trial, compared the benefits of treating women diagnosed with HER2 positive, early-stage breast cancer with 1- or 2 years of, or no, trastuzumab after receiving chemotherapy. At the time HERA was conducted, trastuzumab was known to benefit women with HER2 positive metastatic breast cancer; HERA researchers wanted to gauge its effect on early-stage disease. 

HERA enrolled 5,081 women between December 2001 and March 2005. Of those, 1,694 were assigned to 2 years of trastuzumab; 1,694 to 1 year of trastuzumab; and 1,693 to the observation (no trastuzumab) arm. The dose of trastuzumab was determined by each woman’s weight, and was given by vein. At 1 year of follow up, HERA found that trastuzumab lowered the rate of recurrence by nearly 50 percent when given after chemotherapy.

Herceptin for ILC versus IDC Trial

Between 10 to 15 percent of breast cancers are ILC. Though often treated similarly, ILC has different qualities and patterns of behavior than IDC. ILC occurs more often in both breasts, called bilateral breast cancer, and tends to be less responsive to chemotherapy. It is also mostly estrogen receptor-positive (ER positive) and HER2 negative.

When ILC is HER2 positive, survival outcomes for women are worse than for those with HER2 negative, ER positive ILC. Researchers of the current study did an analysis using existing data from the HERA trial to find out if trastuzumab differently impacts HER2 positive ILC or HER2 positive IDC.


The current analysis used only the 3,401 women enrolled in HERA’s observation and 1-year treatment arms. Within the group

  • 94.5 percent had IDC.
  •   5.5 percent had ILC.

The researchers compared the two groups by the percentage of estrogen and progesterone receptors seen, the rate of HER2 protein increasing in the cells, and the type of breast cancer-free event experienced, as defined in HERA. In addition, they considered overall survival (OS), the time from starting the study treatment to death from any cause.


Comparing the ILC and IDC groups, the researchers learned that ILC and IDC had similar benefits from treatment with trastuzumab, with no differences in DFS or OS. Because of the rates that HER2 protein increased in both ILC and IDC, they responded equally well to treatment with Herceptin. In addition, they found 

  • ILC had higher numbers of estrogen and progesterone receptors than IDC.
  • IDC had higher rates of high (greater than 18) rates of HER2 protein increasing in the cells than ILC.
  • ILC and IDC had similar rates of middle (10 to 18) rates of HER2 protein increasing in the cells.  
  • ILC and IDC had similar occurrences of breast cancer-free survival events.
  • ILC and IDC had similar benefits from treatment with trastuzumab, with no differences in DFS or OS.


In the HERA trial, tumor samples were analyzed individually rather than through central pathology review. In clinical trials, central pathology review requires all tissue samples to be tested by the same lab to ensure they have all been tested and classified in the same way. Not using central pathology review can sometimes lead to less accurate results. In addition, the HERA data did not include the subtypes of ILC samples, so the current researchers were not able to explore whether certain subtypes are more likely to be HER2 positive.

What This Means for You

Because HER2 positive ILC and IDC responded equally well to treatment with trastuzumab after chemotherapy, the authors recommend that women diagnosed with early-stage, HER2 positive lobular breast cancer or ductal breast cancer be offered 1 year of treatment with trastuzumab. In the past, some doctors may have tested lobular cancer for HER2 status less often because it is less likely to be HER2 positive; based on these findings, testing lobular tumors for HER2 status is suggested. 

Your doctors should assess the cancer’s HER2 status and note it in your pathology report. If you have lobular breast cancer and do not know your HER2 status, talk with your healthcare team about the possibility of having your status checked. If the cancer tests HER2 positive, your doctor may suggest 1 year of treatment with trastuzumab to help protect against recurrence. 

Metzger-Filho, O, Procter, M, de Azambuja, E, et al. Magnitude of Trastuzumab benefit in patients with HER2-positive, invasive lobular carcinoma: Results from the HERA trial. Journal of Clinical Oncology. 2013;31(16):1954-1960.

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