Testing treatment: A new look at less common cancer

When it comes to treating breast cancer, Pitt researchers say there won’t be a one size fits all solution.

Physicians at Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute (UPCI) are testing the effects the three most common anti-estrogen treatments for breast cancer have on invasive lobular carcinoma. According to the physician researchers, ILC is a less common form of breast cancer than the more well-known and understood form of breast cancer, invasive ductal carcinoma.

According to the American Cancer Society, about 180,000 new cases of invasive breast cancer doctors have diagnosed in the United States this year. Dr. Rachel Jankowitz, the trial’s principal investigator, said ILC affects about 5 percent to 15 percent of these breast cancer patients, and physicians often treat ILC no differently when it comes to treatment.

“Currently, there is a one-size-fits-all approach in how we treat patients with invasive lobular breast cancer and invasive ductal carcinoma,” Jankowitz said in a UPMC release

Physician researchers like Sheffi Oesterreich, a professor of pharmacology and chemical biology at Pitt, launched the trial that began two to three weeks ago at Magee and the University of Pittsburgh Cancer Institute. Oesterreich expects the trial will enroll 150 participants, which the researchers will randomly divide into three equal therapeutic groups.

Each group will receive one of three common anti-estrogen drugs, which the participants will take during a 21-day period before surgery. The drugs each work differently in the body: Tamoxifen is an estrogen receptor modulator, Anastrozole inhibits the enzyme that synthesizes estrogen and Fulvestrant is a complete estrogen receptor blocker. 

“Our trial will examine how ILC tumor tissue responds to the current standards of care — treatment with either Tamoxifen or Anastrozole, as compared to Fulvestrant, a drug currently approved only to treat advanced breast cancer,” Oesterreich said.

After the research, Jankowitz said she wants to develop a better treatment plan that targets ILC specifically.

“Our goal is to increase understanding of how to tailor treatment for women with ILC in order to ultimately improve their long-term outcomes,” Jankowitz said.

Jankowitz hypothesizes, based on pre-trial studies, that Fulvestrant may be more effective than the other two drugs. She expects some patients may even be resistant to Tamoxifen.

Jankowitz said ILC differs from the more common invasive ductal carcinoma in its presentation and appearance under the microscope. 

Oesterreich, who will analyze the breast tumor tissues after the therapies, said breast cancer usually presents as a lump of cells, whereas ILC presents as a line or web-like projection of cells. The projection of cells is harder to detect than a lump, Oesterreich said.

Risk factors for ILC are similar to those of invasive ductal carcinomas and include hormone replacement therapies, older age, a rare genetic mutation and late age of first birth.

Oesterreich said most breast cancer research, thus far, has not focused on patients with ILC or has excluded patients with ILC because the disease is so different.

According to Oesterreich, the physicians will obtain a specimen from each participant’s tumor before beginning the 21-day treatment period with one of the three experimental drugs. Once this period ends, surgeons will remove and test the patient’s tumor to see if the cancer persists.

Researchers will examine the tumor again for signs of ILC and examine gene expression, mutations, genetic changes and cell growth due to the drug treatment.

“Our goal is to identify biomarkers in primary tumors, which will tell us which tumors will respond to which endocrine treatment,” Oesterreich said. 

Jankowitz said the researchers will look at changes in the tumor tissue in response to the drug treatment. 

“The proliferation of KI-67 [a cellular marker] will tell us how rapidly the tissue is dividing,” Jankowitz said.

Jankowitz and her team will determine how effective a drug is by how much inhibition of KI-76 occurs. More inhibition would mean less tumor growth.

Jankowitz’s team plans to expand the trial from Magee to cancer centers through the Translational Breast Cancer Research Consortium, which consists of 15 facilities, including UPCI. Jankowitz said her goal is to complete the trial within two years, but if fewer sites offer the trial, the research will take more time.

Jankowitz said this trial will help clear up confusion about why each drug affects a patient in certain ways.

“It will be a big impact,”  Jankowitz said.  “[Our] hope is not only to show that one drug wins, but to know why.”