Invasive Lobular Carcinoma
Invasive lobular carcinoma (ILC) is a rare type of breast cancer that grows in the lobes of the breast, where milk is produced.
Like most breast cancers, it starts the terminal duct lobular units (TDLUs) of the breast, where the lobes meet with the ducts, which carry milk to the nipple.
When cells in the TDLUs first mutate and become cancerous, a few lose the ability to produce a molecule called E-cadherin. This molecule helps healthy breast cells stay attached to their surroundings.
Cancerous cells without E-cadherin tend to migrate toward the lobules. The lack of E-cadherin is a defining feature of ILC.
About 10%-15% of breast cancers are lobular. The rest are ductal.
Because most breast cancer are ductal, breast cancer research and treatment plans historically have not distinguished between the two diseases. There are some important differences in how invasive lobular is treated and behaves, and researchers are now studying ILC more closely.
Unlike ductal carcinomas, ILCs usually do not form a lump. Instead, the cancer cells grow in straight lines. This makes them harder to feel during a physical breast examination. In many cases, patients do not notice the growth until these lines of cancer cells intersect and form a mass.
When this occurs, the tumor often feels like a swollen, full breast and not a lump.
Compared to ductal breast cancers, ILC is more often low-grade. This means the cancer cells look similar to normal, healthy cells. Low-grade cancers typically grow and spread more slowly than high-grade cancers.
As a low-grade cancer, the prognosis for early-stage ILC is generally good. However, the disease has a higher chance of returning after 10 years than invasive ductal carcinoma.
When ILC spreads, or metastasizes, it often moves into gastrointestinal tract, ovaries, peritoneum, retroperitoneum and leptomeninges (part of the membrane that surrounds and protects the brain and spinal cord).
Molecular receptors and invasive lobular carcinoma
Receptors are molecules that cancer cells produce inside the cell or on the cell’s surface. These receptors can interact or bind with specific proteins and hormones in the patient’s body. This is called recognition.
Researchers have identified certain receptors that fuel the growth and spread of breast cancer when they recognize a specific molecule. By interrupting this recognition with cancer drugs, the disease’s growth can be slowed or stopped.
To date, doctors have identified three molecular subtypes that play important roles in the patient’s prognosis and treatment: human epidermal growth factor receptor 2 (HER2), and receptors for the hormones estrogen and progesterone.
Most ILCs are positive for the estrogen and progesterone receptors and negative for the HER2 receptor. They are called hormone-receptor positive breast cancers.
Historically, two breast cancer subtypes known as invasive lobular carcinoma and ductal carcinoma have been grouped together. They’ve been thought of as having the same screening needs, symptoms, genetic drivers and treatment. But that’s a mistake.
A recently published comprehensive review and new research being presented at the 2022 American Society of Clinical Oncology Annual Meeting (ASCO) by breast medical oncologist Jason Mouabbi, M.D., is helping to distinguish invasive lobular carcinoma as its own subtype and define more tailored treatment approaches.
Invasive lobular carcinoma is different from ductal carcinoma
Invasive lobular carcinoma, also called lobular breast cancer, forms in the cells of the breast that produce milk. These cells are called lobules. When breast cancer occurs in the cells of the milk ducts and/or the nipple, the diagnosis is classified as ductal carcinoma.
“These cells have such different functions. How could we study them as one?” Mouabbi says. Though both occur in the breast, the diagnoses are very different.
Invasive lobular carcinoma isn’t rare
Lobular breast cancer accounts for only 10% of breast cancer cases in the United States. It’s been seen as impractical to study the subtype separately, Mouabbi says.
However, 40,000 women will face a lobular breast cancer diagnosis this year. That’s more cases than ovarian and cervical cancer, which are estimated to have 29,000 and 19,000 cases this year, respectively.
“It’s wrong to say it's a small proportion of cancers,” Mouabbi argues. “It’s a small portion of breast cancers, but it’s a sizable population facing this diagnosis each year.” Because of the number of diagnoses each year, Mouabbi says it’s important to conduct studies devoted to the subtype to improve care. “It needs to have more attention so we can find better screening, better detection and better therapies,” Mouabbi says.
Lobular breast cancer doesn’t always present as a mass
“It’s a myth that breast cancer always shows up as a mass,” Mouabbi says. While ductal breast cancer grows like an onion, lobular breast cancer doesn’t.
“One of the hallmarks of lobular breast cancer is that it loses its anchoring protein,” Mouabbi says. The cancer cells don’t link with surrounding cells so they grow in lines. Eventually, the lines of cancer cells cross and interconnect to form a mass, but at that point, the cancer is advanced.
Because the cancer doesn’t grow as a mass, patients often can’t feel it. Those who do report their breast feel denser or they see their nipple retract.
Mammograms and ultrasounds also aren’t effective in detecting the cancer because of its cell growth pattern. The best screening approach is a breast MRI, which isn’t standard of care.
“Until MRI becomes more widely used, I’m afraid that lobular cancer is going to be underdetected,” Mouabbi says.
Because detection is challenging and patients don’t see changes in their breast, 60% to 70% of patients’ diagnoses are changed to a higher stage after surgery.
Mouabbi says it’s common for patients to be initially diagnosed with a mass that’s less than 1 centimeter but is found to be much larger at surgery.
Lobular breast cancer spreads to the gastrointestinal and urinary tracts
Lobular breast cancer tends to spread to unusual sites, such as the lining of the gastrointestinal and urinary tracts. Patients often notice they feel constipated or have changes with urination.
Like in the breast, the cancer cells grow linearly and cause these tracts to narrow. “It’s like a lasso that tightens over time,” Mouabbi says.
Because the cells grow in sheets and not a mass, metastasis is also difficult to detect.
Family history can help determine risk of lobular breast cancer
There are trends that can help identify people are at higher risk for invasive lobular carcinoma.
Individuals with a family member who has also been diagnosed with the disease are at a higher risk of the same diagnosis, Mouabbi says.
In addition, people with a family history of stomach cancer face a greater risk of lobular breast cancer. “It’s the same mutation fueling the cancers,” Mouabbi says.
Lastly, the precancerous lesion known as lobular carcinoma in situ (LCIS) can increase a person’s chances of a lobular breast cancer diagnosis. With LCIS, the abnormal cells grow inside the lobule, but because they’re contained, it’s considered premalignant. They can also become calcified, which allows detection with a mammogram and surgical removal. “But patients often aren’t aware that LCIS spots increase their risk of lobular breast cancer in both breasts,” Mouabbi says.
Standard of care treatment not tailored to invasive lobular carcinoma
To help identify lobular breast cancer early, Mouabbi urges patients who fall into these categories be monitored with an MRI rather than an ultrasound.
Many patients with invasive lobular carcinoma receive the standard-of-care chemotherapy, but the comprehensive review showed there isn’t much clinical benefit. That’s because it has been based on clinical trials combining lobular and ductal breast cancer. “All the conclusions from these studies are driven by ductal carcinoma,” Mouabbi says. “We need something different for these patients.”
He adds that prognostic tools such as Oncotype DX and MammaPrint are not very useful in invasive lobular carcinoma for the same reasons. “While it’s been thought that invasive lobular has a favorable prognosis when compared to ductal carcinoma, our review showed that’s not true in the long-term,” Mouabbi says.
Endocrine therapy is effective in treating invasive lobular carcinoma
There are other therapies for invasive lobular carcinoma, but they’re not widely used yet. For example, the review led by Mouabbi found that 95% of lobular breast cancers are hormone-driven, while only about 50% of ductal breast cancer are. Because of this, lobular breast cancer can be treated with endocrine therapy.
Also, lobular breast cancer appears to be immunologically hot. That means the immune system recognizes the tumor. Mouabbi hopes to open clinical trials at MD Anderson soon to investigate treating these cancers with immunotherapy.
Other opportunities lie in the genomic makeup of the cancer. “We found that lobular breast cancers are universally driven by the CDH1 mutation,” Mouabbi says. They also found almost 15% of patients carry the HER2 gene mutation, and 60% carry the PIK3CA gene mutation.
“It’s exciting because we’ve identified targets that may lead to more effective treatment,” Mouabbi says. And the mutations are present at conception. This means targeted therapies could be an option for initial treatment. The retrospective analysis being presented by Mouabbi at the 2022 ASCO Annual Meeting reveals targeted therapy outcomes in patients with lobular breast cancer. “We found that patients benefit from a combination of targeted therapy and endocrine therapy,” Mouabbi says.
Invasive lobular carcinoma clinical trials are critical for progress
To define more personalized approaches, Mouabbi says it’s critical to conduct clinical trials specific to lobular breast cancer. Or, if clinical trials are combined, the patients must be protected with a cohort specific to the subtype.
“If there’s a clinical trial specific to lobular breast cancer, I urge patients to consider enrolling,” Mouabbi says. “It all starts by building more awareness about this disease.”
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
Invasive lobular carcinoma risk factors
A risk factor is anything that increases a person’s chance of developing a particular disease. The risk factors for ILC include:
- A family history of ILC or of stomach cancer. The same gene, CDH1, causes both cancers, so having one of these diseases in your family increases your risk for ILC.
- Lobular carcinoma in situ: This is a precancerous condition in which potentially cancerous cells have formed but haven’t invaded nearby tissue. Only about one in five cases develop into ILC.
- Genetic conditions: Most patients with ILC have a somatic (not-inherited) mutation to the CDH1 gene, which makes E-cadherin when healthy. Some ILC patients have familial (inherited) CDH1 mutations, which presents with other cancers such as diffused gastric cancer. Learn more about hereditary cancer syndromes.
- Post-menopausal hormone therapy: Women who have received hormone therapy to treat post-menopausal symptoms are at an increased risk of ILC.
- Biological sex: Females have a higher chance of developing ILC than males. Males do have lobules in their breasts, so they can develop the disease, though.
Invasive lobular carcinoma symptoms
Breast cancer symptoms vary from person to person. The best thing to do is to be familiar with your breasts so you know how “normal” feels and looks. If you notice any changes, tell your doctor. While regular self-exams are important, many breast cancers are found through regular screening exams before any symptoms appear.
The symptoms of ILC include:
- A breast that feels swollen, thick or full
- A newly inverted nipple
- Skin dimpling
- An orange peel texture on breast skin
- Nipple discharge
- A red, scaly nipple
These symptoms do not always mean you have breast cancer. However, it is important to discuss any symptoms with your doctor, since they may also signal other health problems.
Some cases of breast cancer can be passed down from one generation to the next. Genetic counseling may be right for you. Learn more about the risk to you and your family in our prevention and screening section.
Invasive lobular carcinoma diagnosis
An accurate diagnosis is the first step in successful treatment for ILC. The following tests may be used as screening and/or diagnostic tests for ILC. They can also show if the cancer has spread and monitor how the disease is responding to treatment.
Imaging exams: Imaging exams are used to look for cancer inside the body. They can help locate tumors and track how the body is responding to treatment. There are many types of imaging exams. The ones used for ILC include:
- Mammogram: A mammogram uses X-ray images of the breast taken from different angles to look for growths in the breast. Mammograms are the standard screening exam for breast cancer. Because ILCs typically do not form lumps, they can be more difficult to detect than ductal carcinoma in a standard mammogram. People with risk factors for ILC instead should request a contrast-enhanced digital mammogram (CEM). These tests use an intravenous (IV) dye to improve the ability to see cancers. They are about as accurate as an MRI of the breast and have a much lower rate of false positives. CEMs are performed at MD Anderson but are not widely available. Learn more about CEMs.
- MRI: Magnetic resonance imaging, or MRI, uses magnetic fields and radio waves to generate pictures of the body’s soft tissue and organs. Because ILC does not form a lump like most other breast cancers, MRIs are more effective at identifying these tumors than standard mammograms. They are more widely available than CEM exams.
Biopsy: During a biopsy, a small tissue sample is removed and examined under a microscope for the presence of cancer cells. Depending on tumor location, some biopsies can be done on an outpatient basis with only local anesthesia.
For breast cancer, patients usually undergo an image-guided core needle biopsy. During this procedure, a live image of the breast tissue is used to help doctors guide the needle to the suspected cancer tissue. In many cases, this biopsy is performed during the initial imaging exam in order to speed up the diagnosis.
If the biopsy reveals cancerous tissue, additional images and biopsies may be needed to determine the exact type and extent of the disease. This part of the diagnosis shows whether the cancer has spread to nearby lymph nodes or other parts of the body.
Blood tests: These tests can help monitor the disease and the patient’s response to treatment.
Molecular diagnosis: If the patient is diagnosed with breast cancer, doctors will also analyze the cancer cells to determine the disease’s molecular receptor subtype. By understanding the subtype, they can develop a comprehensive, personalized treatment plan.
Most ILCs are positive for the estrogen and progesterone receptors and negative for the HER2 receptor. They are called hormone-receptor positive breast cancers.
Patients with suspected ILC will also be tested for the loss of E-cadherin. The absence of this molecule is a defining feature of the disease.
Invasive lobular carcinoma treatment
Treatments for ILC include:
Surgery
Most women diagnosed with ILC get surgery to remove the growth. Patients undergo one of the following procedures:
- Lumpectomy: In a lumpectomy surgery, the tumor and a small amount of surrounding healthy tissue are removed. This procedure may be used for early breast cancer cases where the tumor is still small. Lumpectomies are usually outpatient procedures and have shorter recovery times.
- Mastectomy: In a typical mastectomy, the entire breast with the tumor is removed. There are several different types of mastectomies, including procedures that let the patient keep the breast’s skin and nipple/areola. Often a mastectomy and breast reconstruction can be performed in the same procedure.
Hormone therapy
Many breast cancers have high levels of hormone receptors on or in the cancer cells. When these receptors interact with hormones, they send signals to the cancer cells to rapidly grow and multiply. Hormone therapy interferes with this interaction, slowing or stopping the growth of cancer.
Most ILCs have high levels of the receptor for the female hormone estrogen. Patients with these cancers receive hormone therapy, which blocks the interaction of estrogen with the cancer cells’ estrogen receptors or lowers the body’s natural estrogen production.
Targeted therapy
Targeted therapy drugs are designed to stop or slow the growth or spread of cancer. This happens on a cellular level. Cancer cells need specific molecules (often in the form of proteins) to survive, multiply and spread. These molecules are usually made by the genes that cause cancer, as well as the cells themselves. Targeted therapies are designed to interfere with, or target, these molecules or the cancer-causing genes that create them.
Learn more about targeted therapy.
Chemotherapy
Chemotherapy drugs kill cancer cells, control their growth or relieve disease-related symptoms. Chemotherapy may involve a single drug or a combination of two or more drugs, depending on the type of cancer and how fast it is growing.
Learn more about chemotherapy.
Radiation Therapy
Radiation therapy uses powerful, focused beams of energy to kill cancer cells. There are several different radiation therapy techniques. Doctors can use these to accurately target a tumor while minimizing damage to healthy tissue.
Why choose MD Anderson for your invasive lobular carcinoma treatment?
Choosing the right hospital may be the most important decision you make as an ILC patient. At MD Anderson you’ll get treatment from one of the nation’s top-ranked cancer centers.
Because ILC is a rare disease, it is often treated like more common breast cancers. The team at the Nellie B. Connally Breast Center includes doctors who specialize in treating ILC. They work together to develop treatment plans tailored to this specific cancer and to each individual patient. These treatments are designed to eliminate the cancer and maximize your quality of life.
This care is available beyond MD Anderson’s campus in the Texas Medical Center. Through our Houston-area locations, patients throughout the region can get the same multidisciplinary care and personalized attention close to home.
As a top-ranked cancer hospital, MD Anderson is also a leader in innovating new and better ways to treat ILC. Our physicians are developing some of the first clinical trials dedicated to ILC patients.
And at MD Anderson you will be surrounded by the strength of one of the nation's largest and most experienced cancer centers. From support groups to counseling to integrative medicine care, we have all the services needed to treat not just the disease, but the whole person.