Learn more about DCIS and how BCRF is advancing research to understand and treat “stage 0” breast cancer

Breast cancer is the most common cancer in women living in the U.S. Of all breast cancer diagnoses in the country, 20-25 percent are ductal carcinoma in situ (DCIS). The American Cancer Society estimates that about 51,400 new cases of DCIS will be diagnosed in women this year.

Though it can be very stressful and alarming, DCIS is not life-threatening—practically all patients with stage 0 breast cancer can be cured. Having DCIS can, however, increase one’s risk of developing invasive breast cancer. Currently, there is not a way to determine which DCIS cases will become invasive breast cancer and which will not, so DCIS is almost always treated.

Read on to learn what DCIS is and its symptoms, how it is diagnosed and treated, and how BCRF researchers are improving care and learning more about this form of breast cancer.

What is Ductal Carcinoma in Situ (DCIS)?

Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer, which is why it’s sometimes referred to as stage 0 breast cancer. DCIS, by definition, is cancer that starts in the cells lining the milk ducts (carcinoma) and remains in the area where it originates (in situ). DCIS remains in the milk duct and does not spread through the duct walls into the surrounding breast tissue. Stage 0 breast cancer is considered to be a precursor to invasive, stage 1–4 breast cancers.

Although DCIS is defined by the area in which it occurs, the lesions can significantly differ from patient to patient and can vary in molecular and histological features, genetics, clinical presentation, and potential to progress to invasive breast cancer. DCIS is classified into the same molecular subtypes as invasive breast cancer. More about DCIS classification is discussed with regard to DCIS diagnosis below.

DCIS vs. LCIS

Similar to ductal carcinoma in situ, lobular carcinoma in situ begins—and remains—in the cells that line the breast lobules (the glands that make milk). While DCIS is the most common type of non-invasive breast cancer, LCIS is much rarer and accounts for approximately 0.5–4 percent of breast biopsies.

Interestingly, unlike DCIS, researchers have observed that LCIS is not a precursor to invasive breast cancer. Rather, it’s considered a marker for increased breast cancer risk, much like family history. For this reason, some experts prefer the term “lobular neoplasia”—neoplasia meaning abnormal growth of cells that can be benign—instead of “lobular carcinoma.” After surgical removal of the lesion, LCIS patients typically undergo observation rather than further treatment.

Are there DCIS symptoms? How is DCIS diagnosed?

Most people will not experience any DCIS symptoms. In rare cases, women may feel a lump in their breast or have nipple discharge. But typically, DCIS is found on a mammogram.

DCIS diagnosis has increased significantly since routine screening mammograms became widespread. Before screening mammography, less than five percent of newly diagnosed breast cancers were DCIS, whereas now 20-25 percent of diagnosed breast cancers are DCIS. From 1973–1975, before routine mammography, the incidence of DCIS was 1.87 per 100,000 people screened. This rose dramatically to 32.5 by 2004 and has since plateaued.

When a radiologist reads a screening mammogram, they usually identify DCIS by the appearance of microcalcifications that are either localized or widespread and have irregular shapes and sizes. An additional diagnostic mammogram is usually recommended, which takes images at higher magnification from more angles. This mammogram evaluates both breasts and provides a closer look at the microcalcifications to determine whether they are a cause for concern. If the area in question needs further evaluation, additional imaging may be done followed by breast biopsy.

DCIS diagnosis is ultimately confirmed by biopsy; tissue is removed and sent to the lab for analysis. DCIS can vary in its structural features and genetics, which adds complexity to diagnosis and has led to multiple systems for classification.

Typically, DCIS is categorized by what’s called nuclear grade, which measures the characteristics of the nuclei of the cells like size and shape compared to the nuclei of normal breast cells. DCIS is categorized as low-grade (grade I), intermediate grade (grade II), or high-grade (grade III). The higher the grade, the more abnormal the nuclei and the more aggressive and fast-growing the cancer cells.

Each of the molecular subtypes of invasive breast cancer can be identified in DCIS, but the prevalence of each is different. In particular, triple-negative and similar, basal-like subtypes are uncommon in DCIS. DCIS is a key intermediate in the progression to invasive breast cancer, but different subtypes grow at different rates, and not all breast cancers appear to have a long-lived DCIS stage—notably, triple-negative breast cancer. Research suggests that the rapid tumor progression that is a hallmark of triple-negative breast tumors means that there is seldom triple-negative DCIS at the time of diagnosis.

DCIS treatment

DCIS treatment has a high success rate, in most cases removing the tumor and preventing recurrence. The prognosis is excellent—98 percent survival after 10 years.

For most people, the disease is localized to a small area and DCIS treatment includes breast-conserving surgery (lumpectomy). If the DCIS is widespread relative to the area of the breast or is multifocal (occurring in more than one area of the breast), mastectomy is recommended, and no further treatment is needed in most cases.

Lumpectomy is usually then followed by radiation therapy. Any remaining abnormal cells are killed with high-energy beams, such as X-ray or proton. Radiation therapy after lumpectomy reduces the chance that DCIS will recur or that it will progress to invasive cancer. Radiation following lumpectomy is not necessary in some instances, such as if the area of DCIS is small and low-grade.

Hormone therapy may be given after surgery or radiation in some cases of hormone receptor–positive DCIS to decrease the risk of future invasive breast cancer.

Is DCIS cancer? Should DCIS be treated like invasive breast cancer?

DCIS is considered pre-invasive and an early form of breast cancer because the cells inside the duct are cancerous. However, DCIS treatment is controversial and remains a clinical challenge. If left untreated, some cases of DCIS will transform into invasive breast cancer, but it is uncertain how many. Estimates of DCIS cases that will become invasive breast cancer range from 20-50 percent. Put another way, 50-80 percent of DCIS cases will not become invasive.

Currently, our ability to stratify DCIS by risk is in its early stages. At this point, the standard of care is to reduce risk as much as possible by treating DCIS like early-stage breast cancer, typically with the combination of surgery, radiation, and hormone therapy depending on the case. These treatments are recommended because they have been shown in clinical trials to decrease the risk of developing an invasive breast cancer in the future; however, the 10-year survival rate for a DCIS diagnosis is very high (at 98 percent) regardless of whether treatment is given after surgery. Because DCIS treatment does not improve survival, researchers, clinicians, and others have raised concerns that DCIS may be overtreated and debated whether treatment benefits outweigh impacts on quality of life.

Clinicians and patients, then, face the dilemma of having to weigh these risks versus benefits. DCIS can be costly and take a physical and emotional toll on a patient. At this time, it is not possible to predict which cases of DCIS will become invasive breast cancer and which will not, which is why research into DCIS is so needed.

BCRF Research into DCIS

BCRF is the largest private funder of breast cancer research in the world and is dedicated to improving our understanding of all stages of the disease. Compared to invasive breast cancer, DCIS has been understudied, resulting in uncertainties about the best ways to manage individual diagnoses.

RELATED: New Ductal Carcinoma In Situ Research Developments Presented at SABCS 2020

BCRF investigators are working to understand how DCIS progresses to invasive disease, to predict which DCIS cases will become invasive breast cancer, and to improve DCIS treatment by:

  • Conducting a clinical trial for low-risk DCIS comparing close monitoring (via screening) to standard-of-care treatment to find predictors of invasive disease
  • Identifying biomarkers that predict low vs. high risk of DCIS progression to invasive breast cancer
  • Studying the immune landscape of DCIS and how cancer cells escape surveillance to become invasive breast cancer
  • Analyzing cells that line the milk ducts to understand their role in preventing immune cells from blocking DCIS
  • Developing a method to determine how the age of DCIS lesions can be used to predict aggressiveness and inform treatment decisions

Through these investigations, BCRF researchers are hoping to gain new insights into stage 0 breast cancer and prevent overtreatment. Understanding the process by which DCIS becomes invasive breast cancer and uncovering predictors of progression are critical to improving treatment guidelines—and may even offer insights into breast cancer’s origins.

References
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