Invasive Lobular Carcinoma: Symptoms, Diagnosis, and Prognosis
Learn more about invasive lobular carcinoma symptoms, diagnosis, treatment, and what BCRF is doing to accelerate lifesaving research
Key Takeaways
- Invasive lobular carcinoma (ILC) is the second most common type of breast cancer. It accounts for 10 to 15% of invasive cases, and it’s becoming more common.
- Endocrine therapy is the mainstay of treatment, although tumors can become resistant over time.
- ILC often grows in single-file lines (linear pattern) rather than a lump (lobular pattern), so it may not show up clearly on a mammogram or during a breast exam. MRI may detect it more reliably.
- When caught early, the outlook is very good. The five-year relative survival rate is 99% for breast cancers found at a localized stage.
- ILC can return or spread many years after treatment, sometimes to unusual sites such as the ovaries, gastrointestinal tract, or abdominal lining.
- BCRF-funded scientists are studying ILC’s unique biology, new HER2-targeted options, and better detection tools to improve outcomes.
Invasive lobular carcinoma (ILC), also called invasive lobular breast cancer or simply lobular carcinoma/breast cancer, is the second most common type of breast cancer after invasive ductal carcinoma (IDC). The difference is where the cancer starts. Ductal carcinoma begins in the milk ducts. Lobular carcinoma begins in the lobules, the milk-producing glands of the breast.
Lobular breast cancer makes up 10 to 15% of all invasive breast cancers, and it is becoming more common. Incidence rose 2.8% per year between 2012 and 2021, more than three times faster than all other breast cancers combined. About 33,600 women in the U.S. were expected to be diagnosed with lobular breast cancer in 2025.
ILC is treatable, and when it is found early, the outlook is very good. But its unique biology affects how it is detected, diagnosed, and treated. That’s why BCRF, the largest private funder of breast cancer research in the world, has made lobular breast cancer a research priority. In just the last few years, advocates and researchers like BCRF investigator Dr. Steffi Oesterreich have made terrific progress.
What is invasive lobular carcinoma?
Invasive breast cancers have broken out of the area where they started and spread into the surrounding breast tissue. Invasive ductal carcinoma is the most common type, followed by invasive lobular carcinoma.
Hormone receptor and HER2 Status
In fact, 95% of invasive lobular carcinomas are estrogen receptor (ER)-positive, and 70% are progesterone receptor (PR)–positive; 60 to 70% are both. Invasive lobular carcinoma is also typically HER2-negative, meaning the cells make little or no HER2 protein. This profile makes lobular carcinoma a good candidate for endocrine (anti-hormone) therapy.
Who is at risk?
Lifetime exposure to estrogen and progesterone raises the risk of hormone-driven breast cancers like invasive lobular carcinoma. This exposure is shaped by hormone replacement therapy and by age at first period, childbirth, and menopause. Alcohol is a known risk factor for all breast cancers, but it appears to affect lobular carcinoma risk more than invasive ductal carcinoma risk.
Invasive lobular carcinoma is more common in postmenopausal women and tends to be diagnosed at later stages. It is rare in men, making up less than 2% of male breast cancers.
What is the difference between lobular and ductal breast cancer?
In classic invasive lobular carcinoma, tumor cells grow in single-file strands rather than forming the “lump” typical of ductal breast cancer. Other cell variants include solid clusters, honeycomb-like groups (alveolar), tube-like strands (tubulo-lobular), and combinations of these. All grow in a diffuse pattern that barely disturbs the surrounding tissue.
This pattern comes from a change in the CDH1 gene, which makes E-cadherin, a protein that helps cells stick together. Loss of CDH1 is the most common genetic change distinguishing ILC from IDC. It is also linked to tumor growth, invasiveness, and metastasis (spread to distant parts of the body).
What are common symptoms of invasive lobular carcinoma?
ILC may be found through routine screening before any symptoms appear. Its symptoms are similar to those of other breast cancers, but because it tends to form a line rather than a lump, it can be harder to feel during a breast exam. – Talk with your health care provider if you notice:
- A hardened or thickened area in the breast or underarm
- Dimpling, denting, or puckering of the breast skin
- A change in breast size or shape
- Nipple changes, including inversion or pulling to one side
- A new area of fullness or swelling in the breast
How is invasive lobular carcinoma diagnosed?
The diffuse growth pattern of lobular carcinoma can make diagnosis especially challenging. These breast cancers are also more likely to be multifocal (found in more than one place) or bilateral (found in both breasts), which complicates screening, detection, and treatment.
Mammography and ultrasound, the standard breast imaging tools, are less reliable for detecting lobular breast cancer early or catching recurrent disease. This can lead to later detection and a more advanced stage at the time of diagnosis. Current research shows that MRI may detect lobular carcinoma better than mammography, and new screening techniques are being developed, several of which are now in clinical trials.
Invasive lobular carcinoma grades and stages
After diagnosis, your care team will describe the cancer by its grade and stage. Both help guide treatment.
Grade describes how abnormal the cells look and how quickly they are likely to grow. Invasive lobular carcinoma is graded with the Nottingham system:
- Grade 1: Cells look close to normal and grow slowly. In ILC, these tumors often have a cord-like formation and generally have a good prognosis.
- Grade 2: Cells look somewhat abnormal and grow at a moderate pace. Most ILCs are grade 2.
- Grade 3: Cells look very different from normal and grow faster. This is less common in ILC and more often seen in variants such as pleomorphic lobular carcinoma.
Stage describes how far the cancer has spread: localized (breast only), regional (nearby tissue or lymph nodes), or distant (other parts of the body). Stage shapes decisions about surgery, radiation, and systemic therapy, and it is closely tied to prognosis.
Invasive lobular carcinoma prognosis and survival rates
When invasive lobular carcinoma is found and treated early, the prognosis is very good. ILC is generally a slow-growing cancer, which gives patients and their care teams more time to treat it effectively. For breast cancers found at a localized stage, including lobular carcinoma, the 5-year relative survival rate is 99%. Rates begin to decline once the cancer has spread to nearby tissue, lymph nodes, or distant sites.
Invasive lobular carcinoma also has a distinct long-term survival pattern. About 86% of women with ILC are alive and cancer-free 10 years after diagnosis. Five-year survival is similar to other breast cancer types, but at the 10-year mark, survival rates for lobular carcinoma are 4 to 10% lower than other types, partly because it can come back many years later. BCRF investigators are working to understand and close this gap.
Survival rates are population-level statistics based on people diagnosed in the past. They can’t predict any one person’s outcome and may not reflect the latest treatment advances. Talk with your oncologist about what your stage, grade, and tumor biology mean for you.
Where does invasive lobular carcinoma spread?
Like ductal breast cancer, ILC can spread to the bones, lungs, brain, and liver, though this happens less often. Unlike ductal breast cancer, it also tends to spread to the ovaries, gastrointestinal tract, and peritoneum (the lining of the abdomen). Because ILC can return years after treatment, it’s important to know the signs of metastatic disease:
- Persistent, unexplained bone pain, especially in the back, ribs, or thighs
- Unusual pelvic bleeding
- Abdominal pain, swelling, or bloating
- Difficulty eating or digesting food
- Unexplained weight loss
- Shortness of breath or painful breathing
- Frequent headaches, dizziness, or trouble thinking clearly
- Swelling or lumps in the chest, armpit, neck, or groin
- Skin color changes, a lasting rash, or firm skin nodules
- New difficulty seeing
Invasive lobular carcinoma treatment
Breast cancer is usually treated by a multidisciplinary team using surgery, radiation, and systemic therapies. Because invasive lobular carcinoma is diffuse and often multifocal, it is hard to see during surgery, which makes breast-conserving surgery more challenging. Up to 65% of people with lobular carcinoma need a second surgery.
Hormone (endocrine) therapy
Because most invasive lobular carcinomas are hormone receptor (HR)-positive, endocrine therapy is a mainstay of treatment. Tamoxifen is commonly recommended for premenopausal women, along with an aromatase inhibitor such as letrozole or anastrozole for postmenopausal women.
Invasive lobular carcinomaa has generally been treated like HR-positive ductal carcinoma, but its response to hormone therapy differs in important ways. Studies profiling lobular tumors suggest certain genetic mutations can weaken the response and contribute to resistance, and researchers are working to target them. Lobular carcinoma also tends to respond poorly to chemotherapy, which makes understanding its biology critical to better treatment.
The majority of these cancers are hormone receptor (HR)–positive, so endocrine (anti-hormone) therapies are typically administered for lobular breast cancer treatment. Most commonly, the anti-estrogen therapy tamoxifen is recommended for premenopausal women while an aromatase inhibitor such as letrozole or anastrozole is given to postmenopausal women. Although lobular breast cancer responds to hormone therapies, tumors can become resistant to treatment.
Targeted therapy and HER2-low classification
Invasive lobular carcinoma is typically HER2-negative, but a subset of tumors express low levels of HER2. In one large study, about 40% of HER2-negative ILCs were “HER2-low.” Lobular carcinomas rarely have extra copies of the HER2 gene (ERBB2 amplification), which has historically ruled out conventional anti-HER2 therapy. However, HER2-low lobular carcinomas may be a broader target for antibody-drug conjugates, newer drugs that deliver chemotherapy directly to cancer cells and have proven effective in HER2-low breast cancer.
HER2 mutations are found in approximately 10% of invasive lobular carcinoma cases and are linked to endocrine therapy resistance and a worse prognosis. BCRF investigator Dr. Steffi Oesterreich co-authored research showing that targetable HER2 mutations are an independent marker of poorer survival in ER-positive ILC, making HER2-targeted approaches an active area of study.
The need for lobular-specific clinical trials
Because invasive lobular carcinoma makes up a smaller share of breast cancer cases, patients have long been underrepresented in clinical trials, a major barrier to progress. Researchers are working to enroll more people with lobular carcinoma and to design trials focused specifically on this subtype.
BCRF’s lobular breast cancer research
BCRF supports the rapidly growing field of lobular breast cancer research, and recent years have brought exciting progress in tumor biology, technology, and detection. More and more breast cancer clinical trials now include people with lobular disease, and a few are dedicated entirely to it.
Researchers now know that lobular tumors are highly diverse, and this affects how they form and respond to treatment. Scientists have also identified molecular signatures unique to each ILC variant and are developing AI-based tools to spot them in biopsy images. For early detection, molecular tracers that attach to lobular cancer cells are making tumors easier to find on imaging. New laboratory models of ILC are also informing new clinical trials.
BCRF continues to support work to:
- Understand the differences between lobular breast cancer variants
- Identify why invasive lobular carcinoma spreads to uncommon sites such as the ovaries and peritoneum
- Discover biomarkers to target the disease with immunotherapy
- Investigate what drives lobular carcinoma development and growth
- Develop new ways to target and treat lobular breast cancer
In 2016, researchers, doctors, patients, and advocates launched the International Invasive Lobular Carcinoma Symposium, with partial support from BCRF. It was the first meeting focused on lobular breast cancer, and BCRF continues to sponsor it each year.
In 2022, BCRF launched the Leigh Pate Living Biorepository of Invasive Lobular Breast Cancer, a first-of-its-kind repository overseen by BCRF investigators Drs. Steffi Oesterreich, Adrian Lee, and Britta Weigelt. It was made possible through a legacy gift from patient advocate Leigh Pate, founder of the Lobular Breast Cancer Alliance.
BCRF is proud to bring scientists and clinicians together to advance the field and discover new treatments for invasive lobular carcinoma.
Frequently Asked Questions
Most cases of invasive lobular carcinoma are HER2-negative, meaning the tumors express little or no HER2 protein. Within this group, researchers are actively investigating a subset of ILC tumors with low HER2 expression. These HER2-low tumors may be candidates for antibody-drug conjugate therapies, which have proven effective in HER2-low metastatic breast cancers.
ILC tumors are graded 1 through 3 based on how closely cancer cells resemble normal cells. Most ILC tumors are Grade 2; Grade 1 tumors are typically slow-growing with a good prognosis. Grade influences treatment planning and is one factor oncologists use along with stage to guide decisions.
Yes. Lobular breast cancer can recur and spread many years after initial diagnosis and treatment, which makes long-term follow-up important. There is notable discordance between ILC’s low-risk biology and the high tumor burden observed at presentation in many patients, and ILC typically carries a higher risk of late recurrence compared to invasive ductal carcinoma. Patients should discuss a long-term monitoring plan with their care team.
Selected References 
Conquer Cancer. (2021, October 27). Lobular Breast Cancer Alliance: Changing the Conversation on Invasive Lobular Carcinoma. ASCO Connection. Retrieved March 8, 2022, from https://connection.asco.org/magazine/features/lobular-breast-cancer-alliance-changing-conversation-invasive-lobular-carcinoma
Lobular Breast Cancer Alliance. (2018, February 18). ILC fact sheet. The Lobular Breast Cancer Alliance. Retrieved March 8, 2022, from https://lobularbreastcancer.org/ilc-fact-sheet/
McCart Reed, A. E., Kalinowski, L., Simpson, P. T., & Lakhani, S. R. (2021). Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Research, 23(1). https://doi.org/10.1186/s13058-020-01384-6
Wilson, N., Ironside, A., Diana, A., & Oikonomidou, O. (2021). Lobular Breast Cancer: A Review. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.591399
