Invasive lobular carcinoma a distinctive, understudied breast cancer subtype
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Despite being the second most prevalent histologic subtype of invasive breast cancer in the U.S., invasive lobular carcinoma is often detected later and yields worse outcomes than invasive ductal carcinoma, the most common invasive subtype.
Further evidence of the unique features of invasive lobular carcinoma (ILC) has been reported in a study published in Journal of the National Cancer Institute. The multicenter study evaluated more than 33,000 patient records from UPMC Hillman Cancer Center, Cleveland Clinic and The Ohio State University Comprehensive Cancer Center.
The researchers found that ILC and invasive ductal carcinoma (IDC) are biologically distinct diseases and that ILC should be detected and treated differently than IDC.
“There are a number of reasons ILC is not completely understood — one is that it affects fewer patients compared with IDC or cancer of no special subtype, so we haven’t had good models to study it,” study co-lead author Steffi Oesterreich, PhD, co-leader of the Cancer Biology Program at UPMC Hillman Cancer Center, told Healio. “The same has been true in clinical trials. You try to have homogenous populations to draw statistically sound conclusions, and so many trials have had either very few patients with ILC or excluded them.”
A distinct histology
One of the fundamental features of ILC is the loss of a protein called E-cadherin, which helps cells adhere to one another, according to study background. Because of this loss, lobular cancer cells grow in lines, creating tumors that more closely resemble spider webs than the round lumps seen in IDC. This can cause ILC tumors to be more frequently missed on mammography at earlier stages.
“Imaging doesn’t work as well for this subtype, so it is detected later,” Oesterreich said. “The tumors are larger and more frequently include involvement of the lymph nodes. That is concerning, and I think we need to do more toward earlier detection of the disease.”
The study showed that ILC cells had lower grades than IDC cells, with an appearance that is more like that of normal cells. ILC tumors were diagnosed at stage III or stage IV twice as often as their ductal counterparts and larger at diagnosis. Perhaps due to this larger size, women with ILC had higher rates of mastectomy rather than other procedures like lumpectomy.
“It could be that because these tumors are diagnosed at a later stage, we have to have a larger surgery to get the best outcome of clearing the cancer,” study co-senior author Megan Kruse, MD, a breast medical oncology specialist at Cleveland Clinic, told Healio. “The other factor we run into with lobular cancer is sometimes you find multiple spots within the same breast. So, a patient may not have the option of a lumpectomy, because there are smaller cancer spots spread throughout the breast. It might not leave a good cosmetic or functional outcome for the patient.”
Despite the larger size and more advanced stages associated with ILC tumors, they may not benefit similarly from the type of treatments typically deployed on larger, advanced-stage IDC tumors, Kruse said.
“One of the clinical tensions we feel when we’re treating a lobular breast cancer is that many times they are detected at later stages and are larger, and for a patient with a ductal cancer that means we would consider aggressive treatment like chemotherapy,” Kruse said. “Although the stages may be higher, the biology of lobular cancer seems different — it doesn’t grow as quickly, so it is unclear that chemotherapy helps these tumors as much as it impacts more rapidly growing cancers.”
Risk for recurrence
The next part of the study focused on patients with ER-positive, HER2-negative tumors. Investigators found that patients with ILC had worse DFS and OS than those with IDC. Individuals with ILC also had more recurrences.
“An important finding is that very often, these late recurrences in patients with ILC happened up to10 years after the original diagnosis of the primary tumor on the breast,” Oesterreich said.
The researchers also used the commercially available Oncotype DX test (Exact Sciences) to predict recurrence and response to chemotherapy for patients with early-stage, ER-positive, HER2-negative breast cancer.
They found a significant correlation between Oncotype DX score and cancer recurrence for patients with IDC. However, few cases of ILC received a high-risk designation, despite more late recurrences.
Kruse said the researchers plan to further investigate the distinct features of ILC and how it is best detected and treated.
“This study is scratching the surface. Ideally, we would like to dig down deeper into the individual treatments these patients received,” she said. “Right now, we have large categories of treatment, like chemotherapy and antiestrogen therapy, but there are multiple different treatments that fall into those categories. So, having additional granularity of data would be really important.”
Oesterreich emphasized that although ILC has traditionally been addressed similarly to IDC, there has been an increased understanding of and focus on tumor histology.
“When we look at these tumor cells on a microscope, they look different, and when we study the cells in the laboratory, they look different,” she said. “Yet we have not yet been able to translate this into different drugs or treatments. I think that in the future, that’s where we’re headed. That’s the ultimate goal.”
For more information :
Megan Kruse, MD, can be reached at 9500 Euclid Ave., Cleveland, OH 44195; email: krusem@ccf.org.
Steffi Oesterreich, PhD, can be reached at MWRI, 204 Craft Ave., Room B410, Pittsburgh, PA 15213; email: oesterreichs@upmc.edu.
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