Up to 15 percent of U.S. invasive breast cancers are classified as lobular, which refers to the fact that the cancer developed in the cells that line the milk-producing glands (lobules) of the breast. The most common histological type of breast cancer, accounting for approximately 70 percent of cases, is ductal breast cancer, which forms in the milk ducts. Almost half of women diagnosed with lobular breast cancer are treated with mastectomy, either initially or after a lumpectomy that does not result in clean margins.
Lobular cancer is more likely to be multifocal (more than one tumor per breast), bilateral (diagnosed in both breasts at the same time), and both estrogen receptor positive and progesterone receptor positive (ER+/PR+) than ductal breast cancer. It is rare for lobular breast cancer to be HER2 positive. Lobular breast cancer is also more likely to have a hereditary component. In fact, lobular breast cancer patients are more likely to have a father diagnosed with cancer, especially prostate cancer.
Use of hormone replacement therapy (HRT), also known as menopausal hormone therapy, has been shown to increase the risk of lobular breast cancer, as has use of levonorgestrel intrauterine system (LNG-IUS), an IUD-type device. Long-term statin use was also found to be associated with increased risk of lobular breast cancer in one study. Another study reported that long-term use of calcium-channel blockers (a type of high blood pressure drug) more than doubled the risk of lobular breast cancer in postmenopausal women.
Some researchers have suggested that chemotherapy is not useful or even contraindicated for lobular breast cancer. However, this is unproven. One 2015 study reported that treatment with the aromatase inhibitor Femara resulted in better disease-free survival than tamoxifen in women with ER+ lobular breast cancer. In any case, it makes sense that treatment decisions should be based on factors such as tumor size, lymph node status, proliferation index (Ki-67), hormone receptor status, and other prognostic factors in addition to the histological type.
Women with lobular breast cancer are more likely to get ovarian and gastric (stomach) metastases than those with other types of breast cancer.
Women with lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (a possible precursor of both LCIS and invasive breast cancer) are at significantly higher than average risk for invasive breast cancer, but the risk is higher for developing both ductal and lobular breast cancer. LCIS is found in fewer than 2% of all breast cancers. Lobular neoplasia is a global term that refers to both LCIS and atypical lobular hyperplasia.
One small 2015 study reported that 50% of invasive lobular tumors eventually arising in women with LCIS were clonally related, in other words, very similar genetically with shared mutations. A total of 58% of ductal carcinoma in situ (DCIS) lesions developing in women with LCIS were clonally related, but with a lower number of shared mutations than that found in LCIS to lobular cases. No evidence of a clonal relationship was found in any of the cases of invasive ductal breast cancer arising in women with LCIS.
LCIS has familial component
First degree (parent, sibling or child) and second degree (grandparent, aunt/uncle, half-sibling) relatives of women with LCIS have a higher risk of invasive breast cancer than the general population, as one large 2020 Swedish prospective study reported. In fact, the authors found that the 10-year cumulative risk of a 50-year old woman with a first or second degree relative with LCIS was similar to the risk of one with such a relative with invasive breast cancer.
Risk of progression from LCIS to invasive breast cancer
One 2020 study reported that 7.8% of women with atypical hyperplasia and 5.7% of women with LCIS developed invasive breast cancer during the first ten years after diagnosis. A 2017 study reported that the seven-year cumulative invasive breast cancer incidence was 9.9% after an initial diagnosis of atypical hyperplasia or LCIS.
However, the risk of developing invasive breast cancer appears to continue to grow over time. A Canadian study reported that the 20-year cumulative risk of developing invasive breast cancer was 21.3% for LCIS patients. Another study reported that the annual incidence of breast cancer (including DCIS) was 2% among women with LCIS.
A 2015 study concluded that women under age 35 diagnosed with LCIS and other forms of atypical hyperplasia should be followed closely, receiving annual breast cancer screening starting at age 25 or age of diagnosis. This was based on the fact that 12% of such women developed breast cancer within a median of 90 months.
Efforts to predict which LCIS patients will progress to invasive breast cancer have not been very successful. However, one study found that LCIS with high Ki-67 (a marker of proliferation) expression is more likely to progress to invasive breast cancer than low Ki-67. Women with high breast density are also more likely to progress. In addition, LCIS that can be detected manually (palpable LCIS) is more likely to progress to invasive breast cancer. Note that palpable LCIS may feel like an area of thickening or firmness rather than a lump.
Since the majority of women with LCIS do not go on to develop invasive breast cancer, some do not undergo surgery to remove the LCIS lesion. Rather, they are placed under increased surveillance and they may receive endocrine treatment. However, since a substantial minority of women diagnosed with LCIS based on core needle biopsy are found to have invasive breast cancer upon open surgical biopsy, many experts are of the opinion that surgical excision should follow needle biospy to confirm that the diagnosis is limited to noninvasive breast cancer. It is also important for women who do progress to invasive breast cancer to have all of their LCIS surgically removed.
The picture is more clear for pleomorphic lobular carcinoma in situ (PLCIS), a higher-risk type of LCIS which is more likely to progress. When patients are diagnosed with PLCIS using a needle biopsy, the lesion should be surgically removed. In addition, re-excision should be performed if any PLCIS or LCIS is found at or near the surgical margins.
Diagnosing lobular breast cancer
Lobular breast cancer is less visible on mammograms, sonograms and breast MRIs than ductal breast cancer because the cancer cells infiltrate between normal cells in a very regular manner. Typically, lobular breast cancer does not form a discrete lump. Instead, the breast may feel thicker or more firm in the area of the tumor. Because of these factors, lobular breast cancer often is diagnosed when it has reached a larger diameter than other types of breast cancer. Some researchers have recommended that an MRI of both breasts be performed when lobular breast cancer is diagnosed based on a biopsy in order to find other tumors that might be present.
Despite the difficulty in imaging lobular breast cancer, since this type typically does not behave aggressively, lobular breast cancer patients tend to have a relatively good prognosis. On the other hand, lobular breast cancer that is palpable (i.e., can be detected manually) is associated with higher tumor grade and poorer survival than lobular cancer that cannot be felt by hand. Also, lobular breast cancer can relapse many years after initial diagnosis and treatment.
Please see our article on diet for lobular breast cancer patients and survivors information pertaining to diet and supplements. We suggest that LCIS and lobular breast cancer patients and survivors also refer to the articles that discuss their individual breast cancer subtypes (e.g., ER+/PR+, ER+/PR-, triple negative).