All breast cancers initially form inside the milk duct near the area where the duct meets the milk gland, or lobule — a structure called the terminal duct lobular unit. As long as the abnormal cells remain inside the milk duct they are known as carcinoma in situ. When they break out of the milk duct and get into the fatty tissue of the breast, they become invasive breast cancers.
Invasive lobular breast cancers (ILCs) and invasive ductal cancers (IDCs) have very different growth patterns. Invasive lobular cancers tend to grow in single-file lines through the fatty tissue of the breast. Invasive ductal cancers, by contrast, tend to re-form the glandular structures of the breast and are more likely to form a mass.
Is a lump a sign of an invasive lobular breast cancer?
ILC may or may not form a lump. If it’s found by palpating (lightly pressing) the breast, it is more likely to resemble a fullness or thickening in one area that feels different from surrounding parts. On a mammogram, ILC often appears as an area of distortion. The diagnosis is confirmed by performing a biopsy of the tissue in the abnormal area. The majority of ILCs are estrogen receptor-positive (ER-positive), meaning they can use the hormone estrogen to grow.
How is invasive lobular breast cancer treated?
Surgical treatment for invasive breast cancer follows the same approach whether the patient has an invasive lobular or invasive ductal cancer, says Tari King, MD, chief of breast surgery at Dana-Farber Brigham Cancer Center, who has studied both in situ and lobular breast cancers. Most women with invasive breast cancer first undergo surgery to remove the tumor. Depending on the size of the tumor, surgical options may include a lumpectomy (removing just the tumor and a margin of surrounding tissue) or a mastectomy (removing the whole breast). It is also important to determine whether cancer cells have spread from the breast to the lymph nodes under the arm.
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Following surgery, treatment may involve radiation therapy to eliminate any remaining microscopic cancer cells at the site of the tumor, and/or chemotherapy to kill cancer cells that may have escaped into the bloodstream or lymph system. For patients with ER-positive tumors, endocrine therapy to reduce the amount of estrogen in the body or block its effect is also a very effective form of treatment, King says.
What is lobular carcinoma in situ (LCIS)?
Lobular carcinoma in situ (LCIS) is a term used to describe a change in which cells resembling those of invasive breast cancer are contained within the lobule. Although LCIS itself isn’t a form of cancer and is not treated as cancer, it indicates a higher risk of developing breast cancer in the future, in either breast, King says. Women with LCIS have a 20-25 percent risk of developing invasive lobular breast cancer in the future — eight to 10 times higher than in women in the general population.
LCIS isn’t detected by self-examination or routine mammograms. Most diagnoses come about incidentally: the abnormal cells are discovered in a biopsy for another reason in the breast, such as calcifications or benign lumps. For this reason, it’s known as an “incidental finding” and is present in up to 4% of otherwise benign breast biopsies.
Women with LCIS may develop invasive ductal or invasive lobular cancers, with the risk distributed equally in either breast. When breast cancer occurs in women with LCIS, it is almost always ER-positive. This means that medications like tamoxifen, Evista®, and the aromatase inhibitors — which decrease the amount of estrogen in the body or block its action — can be taken to reduce the risk of breast cancer in women with LCIS. Recent data show that these medications may reduce the risk by as much as 70 percent.
“A diagnosis of LCIS doesn’t necessarily mean breast cancer will develop, but it’s important that women diagnosed with the condition be informed of the value of options to reduce breast cancer risk,” King says. “The benefit can be substantial.”
What is some of the latest research in lobular breast cancer?
At Dana-Farber, research in lobular breast cancer is advancing in both the laboratory and the clinic.
In a study in Cancer Research, investigators led by Rinath Jeselsohn, MD, Otto Metzger, MD, and Agostina Nardone, PhD, uncovered a mechanism by which lobular breast cancer can become resistant to the drug tamoxifen. By comparing the molecular workings of ILC cells and IDC cells, they found the lobular cancer cells had a distinct “epigenetic” feature — a change in the levels of a protein that influences gene activity. Specifically, they found that after treatment with tamoxifen, ILC cells had more of the FOXA1 protein bound to chromatin — the DNA-and-protein component of chromosomes. The increase creates an interaction between FOXA1 and the cells’ estrogen receptor, increasing the activity of genes involved in tumor growth and helping the cells resist tamoxifen. The findings suggest that patients with estrogen receptor-positive ILC might benefit from specific hormone-blocking treatments.
The researchers also identified a gene signature — a pattern of gene activity — in a common subtype of lobular breast cancer that was associated with worse outcomes for patients. The subtype, known as luminal A type, is generally a low-risk form of the disease, but some patients develop recurrences years after treatment. The finding may make it possible to identify such patients in advance, although more research is needed to confirm that.
Investigators are analyzing the results of the Palbociclib Endocrine Therapy for Lobular Breast Cancer Preoperative Study, or PELOPS, a clinical trial that compared tamoxifen with aromatase inhibitor treatment in 200 patients with estrogen receptor-positive ILC or IDC prior to surgery. (Tamoxifen blocks estrogen from fueling tumor cell growth, whereas aromatase inhibitors interfere with estrogen production.) The study had two components. In one, patients were randomly assigned to receive either tamoxifen or an aromatase inhibitor for two weeks; in the second, patients were re-randomized to receive either an aromatase inhibitor plus palbociclib (a drug that blocks proteins involved in cancer cell growth and division) or an aromatase inhibitor alone for 24 weeks.
About the Medical Reviewer
Dr. Tari A. King is the Anne E. Dyson Professor of Surgery at Harvard Medical School, the chief of the Division of Breast Surgery and the vice chair of multidisciplinary oncology in the Department of Surgery at Brigham and Women's Hospital, and the chief of breast surgery at Dana-Farber Brigham Cancer Center. She is also the director of the Breast Cancer Personalized Risk Assessment, Education and Prevention (B-PREP) Program at Brigham and Women's Hospital.
Dr. King received her medical degree from University of Colorado Health Sciences Center and completed a general surgery residency at Ochsner Clinic Foundation Hospital (now Ochsner Medical Center) in New Orleans. Dr. King completed both a surgical research fellowship and a breast surgery clinical fellowship at Memorial Sloan Kettering Cancer Center. Her clinical and research efforts focus on improving clinical management strategies for women at high risk of developing breast cancer with a special emphasis on lobular carcinoma in situ and atypical hyperplasia.
Dr. King currently serves on the Steering Committee for the Translational Breast Cancer Research Consortium and is the Treasurer and Chair of the Finance Committee for the Society of Surgical Oncology.