Lobular carcinoma in situ (LCIS): It’s something most women have never heard of—a benign, invisible breast condition with no symptoms—but a diagnosis greatly increases your risk for breast cancer.
LCIS is rare: Between 2007–2011, it was diagnosed in about four out of 100,000 women between in the United States, and it is found in up to four percent of all breast biopsy samples. Incidence is greatest in women aged 40 to 60.
LCIS has unique features that make it different from ductal carcinoma in situ (DCIS) and invasive breast cancers. Knowledge is power and, if you’ve been diagnosed, understanding LCIS is the first step toward managing your personal risk.
LCIS is a condition in which abnormal cells form in the milk-producing glands of the breast called lobules. These cells do not spread beyond the lobule into nearby breast tissue: “in situ” means “in the original place.”
LCIS is classified by its histological features, or the cellular characteristics that can be identified and observed under a microscope. The most common variant is classic LCIS, and cells lining the lobules in samples from those lesions appear smaller than normal cells. Classic LCIS is most commonly seen in pre-menopausal women.
Two rarer LCIS variants have what’s called pleomorphic and florid histology and are observed in fewer than five percent of LCIS cases. In samples of pleomorphic LCIS lesions, cells look larger and irregular compared to normal cells or classic LCIS. In the case of florid LCIS, the cells lining the lobules form a mass with dead cells in the middle.
Cancer is a group of diseases where cells begin to grow uncontrollably. For invasive breast cancer, cells multiply and invade the surrounding breast tissue. The most common form of invasive breast cancer is invasive ductal carcinoma, which begins in the ducts of the breast that carry milk from the lobules to the nipple. The second most common form (10-15 percent of breast cancer diagnoses) is called invasive lobular carcinoma (a.k.a. invasive lobular breast cancer), which begins in the breast lobules.
LCIS is not generally thought to be a precursor to invasive breast cancer. They are more accepted as a marker of increased risk of invasive breast cancer, similar to age or family history. Women who develop breast cancer after an LCIS diagnosis can be diagnosed with either invasive lobular or ductal carcinoma, which can grow in the same breast as the LCIS or in the other breast.
Despite both having lobular in the name, invasive lobular carcinoma and lobular carcinoma in situ (LCIS) are not the same. They just originate in the same place in the breast; invasive lobular carcinoma is breast cancer. Since LCIS is not cancer, some experts prefer using the term “lobular neoplasia”—neoplasia meaning abnormal growth of benign cells— to “lobular carcinoma.”
Lobular neoplasia also includes atypical lobular hyperplasia (ALH), another condition of the breast characterized by an overgrowth of cells that line the lobules or ducts. ALH is not cancer but is linked to a higher risk of developing invasive cancer in the future.
Ductal carcinoma in situ (DCIS) begins in the ducts of the breast like invasive ductal carcinoma. But just as LCIS remains in the lobules, DCIS remains in the ducts and does not spread through its walls to surrounding breast tissue.
DCIS is non-invasive “stage 0” breast cancer, but there is a potential for it to become invasive breast cancer if left untreated. LCIS, on the other hand, is not generally considered an invasive precursor to breast cancer like DCIS. Rather, it can increase your risk of the disease.
The average risk of a woman developing breast cancer in her lifetime is 12 percent. That risk increases to 20 to 30 percent if a woman has been diagnosed with LCIS. The younger a woman is at diagnosis, the higher the risk.
The causes of LCIS are not well known or understood, but some hereditary risk factors have been identified. A gene commonly mutated in LCIS is CDH-1, a tumor suppressor gene that provides the instructions for making the protein E-cadherin. In fact, loss of E-cadherin protein expression is a defining feature of invasive lobular carcinoma.
In some studies, mutations in the PIK3CA gene were found to be just as common as CDH-1 mutations in LCIS. This gene provides the instructions for making the PI3K enzyme, which regulates cell growth, division, and survival.
Researchers continue to investigate genetic mutations and other molecular drivers of LCIS formation and how they may contribute to an elevated breast cancer risk.
Other risk factors for LCIS include being over 40 years of age, using a combination (estrogen and progestin) hormone replacement therapy for more than three to five years after menopause, smoking, and excessive alcohol consumption. These factors are also associated with an elevated risk of developing breast cancer.
LCIS does not usually cause any symptoms. It’s typically diagnosed after a pathologist evaluates breast tissue from a biopsy deemed necessary because of an abnormal mammogram.
Classic LCIS does not usually cause a lump to form or appear on a mammogram, but pleomorphic and florid LCIS can be found this way.
Often, no treatment for LCIS is needed after the biopsy. Because of the elevated cancer risk, doctors may recommend more frequent mammogram, ultrasound, and MRI screenings to ensure any cancer that develops is caught at its earliest stage. Depending on the individual and the LCIS prognosis, they may also recommend hormone therapies that reduce risk, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs).
If the biopsy shows pleomorphic or florid LCIS, doctors may recommend a lumpectomy, a surgery that removes the abnormal cells and a small amount of surrounding healthy tissue. In rare circumstances when a patient’s risk is elevated because of a strong family history of breast cancer or if LCIS is diagnosed at a younger age, a prophylactic bilateral mastectomy, surgery that removes both breasts, may be recommended.
Because no diagnostic tools currently exist that reliably predict who will develop invasive breast cancer after an LCIS diagnosis, it is likely that some women with LCIS are undertreated, and some women are overtreated. Neither scenario is ideal so improving strategies for diagnosis is imperative.
BCRF researchers are committed to developing more precise, personalized breast cancer screening, especially in women who have an elevated risk of breast cancer.
Our investigators are developing a deeper understanding of the drivers of disease by identifying the genetic or molecular biomarkers associated with high-risk breast lesions such as DCIS and LCIS. This knowledge may help explain why some women develop breast cancer and others do not and could potentially lead to better diagnostic tools to predict invasive cancer before it ever develops.
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