Here All Year

Metastatic Lobular Breast Cancer

Help us spread the word… year-round!

Each month, our Here All Year campaign explored a new topic around metastatic breast cancer—from myth and stigma busters, to new research and strategies for improving outcomes. Want to help make a difference for people living with MBC, all year long? Dig deeper into the research, explore the available resources, watch patient stories and share them on your social and email channels.

Metastatic Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is a distinct subtype of breast cancer with unique cellular structures, biology, and behavior. ILC is the 2nd most common type of breast cancer and accounts for up to 15% of all breast cancers including mixed ductal /lobular.  90% of lobular breast cancers are ER/PR+ HER2-, although there are subpopulations that are ER/PR negative, triple negative, or HER2+. This histology can also change over time due to treatment resistance and acquired genomic mutations. In addition to the most common type of Classic ILC, there are special morphological subtypes including Pleomorphic, Solid, Alveolar, and Tubulo-lobular which have different characteristics.

ILC differs from invasive ductal carcinoma (IDC) in that the cells grow in a single file and do not always form a lump or a mass and therefore can be harder to diagnose. ILC has frequent late recurrences and is generally slow growing. Because of ILC’s unique features there are challenges in initial diagnosis, imaging for staging, and clinical trial enrollment.  Importantly, metastatic ILC can travel to unusual sites.

Currently treatment is the same for ILC as IDC , depending on histological subtype. In early stage ILC, studies have shown some evidence that ILC may respond differently than IDC to Tamoxifen and Chemotherapy. Two recent reviews on metastatic breast cancer have shown that CDK4/6 inhibitors and Erubulin (a single agent chemotherapy) show similar efficacy in metastatic ILC when compared to IDC.

ILC has not yet been studied enough to be well understood and more research is needed to refine treatments for people living with metastatic ILC.

This month’s content was developed in collaboration with the Lobular Breast Cancer Alliance (LBCA). The LBCA was founded by patients to raise awareness about ILC and stimulate more ILC research. Their website  provides the most current information about ILC and metastatic ILC and houses a comprehensive ILC publications library. Learn more about ILC and the LBCA at

Click on the image in each section below to read more about the science behind the topic.

Like invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) can metastasize to the bones, lungs, liver, thoracic and abdominal lymph nodes, and brain, but can also spread to unusual sites such as the gastrointestinal tract (i.e., stomach, small intestine, colon), gynecological organs (i.e., ovaries, uterus), the abdominal lining (i.e., peritoneum) and the genito-urinary system (i.e., bladder and ureter).
As with IDC, the most common site of ILC metastases is to the bones. Lung and liver may be less common sites for metastases in ILC than in IDC. However, ILC may travel to tissues such as the Pleura (lining of the lung) and in rarer cases, the Leptomeninges (lining of the brain and spinal cord) and the Orbital canal (tissues behind the eye).
Because of the potential for ILC to metastasize to uncommon sites, it is important for patients with lobular breast cancer and their oncologists to be aware of these differences, and to discuss the importance of recognizing and reporting possible symptoms referring to these unusual sites of metastases.
The linear growth pattern of ILC sometimes makes it difficult  to detect metastatic ILC with current imaging technology such as traditional computed tomography (CT), positron emission tomography (PET) and bone scans. It is well established that primary ILC (in the breast) can be more difficult to detect on imaging than primary IDC. Distant metastases in all breast cancers are more easily seen in the bones, liver, and lungs than in other unusual sites. However, studies are showing that certain types of imaging may be more effective in visualizing different sites of ILC metastases. For example, bone metastases, (the most common site of ILC metastases) may be more visible on integrated FDG PET/CT scans than on CT/ bone scans. There is quite a bit of variety in the efficacy of the types of scans used in relation to different sites of metastases suspected. This makes it extremely important for radiologists to be aware of the ILC histologic subtype when interpreting imaging scans for metastatic disease, and it is also important to note what has proven to work well in each individual patient.
Current research on new types of PET scans are showing promise in ILC. Two early prospective trials on new imaging tracers for PET scans  are demonstrating value at imaging ILC, with some advantages compared to the currently available FDG PET, which targets sugar metabolism. Fluoroestradiol (FES) is a novel imaging tracer (recently FDA approved), based on estrogen expression in ER+ tumors and may also more reliably assess anti-estrogen therapy response than FDG PET/CT.  Fluciclovine (FACBC) targets amino acid metabolism and may also more accurately detect ILC metastases than other imaging methods.
These new tracers could provide improved evaluation of metastases and assessment of treatment responses and could therefore result in improved treatment decisions for patients with ILC.
There are many clinical trials available for patients with metastatic breast cancer but only a few that focus specifically on diagnostic capabilities and treatment options  in metastatic lobular breast cancer.
One of the primary challenges with studying treatment effect is that the typical mechanism used to assess efficacy in clinical trials with metastatic patients, the RECIST criteria, which measures treatment response on CT scan based on “measurable” disease, which is less common in ILC. Due to the diffuse pattern of ILC, it often does not form a mass, making it “unmeasurable,” therefore making these patients ineligible for many trials. In a recent abstract, patients with metastatic ILC were shown to be significantly underrepresented in clinical trials of breast cancer, likely due to the application of RECIST criteria.
Improved staging and/or detection of disease/disease recurrence could result in improved treatment in patients with metastatic ILC. There are current and prospective clinical trials that are using new types of tracers for imaging showing promise in visualizing ILC. There is also potential for using a different criteria called PERCIST, using PET scans for assessing treatment response. These new methods will potentially enable more patients with metastatic ILC to be eligible for clinical trials.
A second key challenge in conducting clinical trials that include a metastatic ILC cohort is that it is frequently harder to find and enroll a sufficient number of patients with ILC. This is because of the relatively lower percentage of patients with ILC as compared to IDC. It is important for more lobular-specific and multicenter trials that include lobular cohorts to increase the numbers of lobular patients. Trials that measure treatment efficacy in ILC will in turn result in more clinical trials being open to patients with metastatic ILC.
Click on the LEARN MORE button below to see existing lobular-specific and lobular-enriched  trials.
While genetic (or germline hereditary ) mutations in certain genes can increase the risk of developing breast cancer, tumors themselves can also acquire genomic mutations that can act as treatment targets. Hereditary mutations in CDH1 can confer a lifetime risk of both ILC and Hereditary Diffuse Gastric Cancer (HDGC). Patients with ILC can also have hereditary mutations in other genes including BRCA2, CHEK2, and PALB2. Currently  there are treatments targeting BRCA mutations (PARP Inhibitors) available for patients with metastatic ILC.
Biomarker testing in tissue or liquid biopsy may be useful in identifying genomic mutations that have approved drugs or are being studied in clinical trials. Many ILC tumors harbor a genomic CDH1 mutation for which there is currently no targeted treatment. There are, however, other genomic mutations that are highly prevalent in lobular tumors, that do have targeted treatments or for which targeted treatments are being studied. For example, approximately 35-50% of lobular tumors harbor the PI3KCA mutation for which there is an approved targeted treatment; Alpelisib (Piqray) for ER+ metastatic patients. Approximately 5-15% of lobular tumors harbor ERBB2 mutations, which occur in the HER2 pathway. Neratinib (an approved drug for HER2+ breast cancers) is being studied for efficacy of treatment in Metastatic ER+ breast cancers with a lobular cohort in an ongoing clinical trial.
Biomarker testing may also be useful in determining anti-estrogen resistance such as the finding of ESR1 mutations, and other mutations such as RB1, which may confer resistance to CDK4/6 inhibitors. In other studies, ILC metastases are showing a higher TMB (tumor mutational burden) score relative to IDC. A TMB score is the number of mutations in a tumor and is used as a biomarker to help determine whether the tumor might respond to treatment with Immune Checkpoint Inhibitors (Immunotherapy).
Other genomic mutations that are prevalent in ILC including FOXA1, AKT1, PTEN, HER2, HER3, ATM, and FGFR mutations are currently being studied in the lab with the expectation that additional targets for treatment may emerge.
Because of the growing understanding about different biomarkers and what they may mean for future treatment for patients with metastatic ILC, it is increasingly common that biopsy of new metastatic sites, biomarker testing conducted either by tissue or liquid biopsy be considered. These tests are done with the hope that they will identify mutations for which there are currently targeted treatments or for which it is expected that there will be in the future.
Ann Camden has been living with metastatic breast cancer since 2016. She is the CEO of the Camden household which includes two rising senior girls, Rose and Grace, and her husband, Jeff … and potentially a new puppy. Ann maintains a blog, Down-Not-Out, where she shares her story with other cancer survivors as well as her family and friends. She is an alumna of Living Beyond Breast Cancer’s Hear My Voice Program and also a volunteer on their helpline. She has been an advocate with the American Cancer Society and METAvivor speaking with local and national legislators. Ann does not turn down an opportunity to talk about her cancer treatments and advocate for additional research dollars aimed toward better treatment options.
Natalia Padron was diagnosed with Stage 3A Breast Cancer in 2013 and MBC in 2015 when she was 48 years old. She is very passionate about helping others and advocating for the Latinx community to help them connect with reliable resources they need. As part of her advocacy with Living Beyond Breast Cancer, she volunteers on their helpline team to support  Spanish-speaking patients struggling with the disease to better understand it and make informed decisions about their treatments and care. She operates Naty Wellness, a business dealing in handmade jewelry and natural soaps that are gentle on skin, something Natalia became interested in after noticing the effects of chemotherapy on her skin. Natalia lives in Florida with her three children, a dog, and two cats.
Jen Heatherly was diagnosed with early stage breast cancer in 2014 and received her MBC diagnosis in 2017. She is an active part of the MBC community and is passionate about helping other cancer patients thrive. She has attended numerous Susan G. Komen live events and lobular breast cancer breakout sessions to stay on top of her disease and to help better advocate for herself and others. In 2018, Jen participated in the Living Beyond Breast Cancer Hear My Voice advocacy program. In 2019, she was chosen as Leslie’s Week Woman of the Month. In June of 2021, part of her cancer journey book “TERMINAL…far from the shallow” was published.
Jen’s motto is to live life in color and minimize the grey moments, so quality of life is vital to her. She loves attending cancer retreats, yoga events, camps, and vacations, and actively posts about her cancer journey on her social media accounts. She uses this as an opportunity to raise funds for many cancer foundations, as well as to inspire and support others who are also fighting this disease.
Kris Blake went through six years of testing before receiving her Lobular Breast Cancer diagnosis. Her cancer was present during her first tests in 2013, but doctors and tests missed diagnosing until 2018. Because of that experience, she is passionate about advocating for MBC and Lobular Breast Cancer patients. Kris says, “If I can help one person to understand lobular breast cancer a little better, I would feel like I’ve made a contribution to this cause.”
Explore Here All Year Project