Importance of Hormonal Treatment Duration for Ductal Carcinoma in Situ Revealed

Two new studies shed light on the best ways to prevent patients with ductal carcinoma in situ (DCIS) from subsequently developing breast cancer and on the complexity of this issue.

One study suggests that at least 2 years of hormone-suppressing therapy (HT) may be needed to provide a lasting benefit in patients with DCIS, while the other suggests that young DCIS patients often choose to forgo hormonal treatment.

Both studies were presented at the American Association for Cancer Research (AACR) Special Conference entitled “Rethinking DCIS: An Opportunity for Prevention?”

What Is Ductal Carcinoma in Situ (DCIS)?

Ductal carcinoma in situ (Ductal Carcinoma In Situ, DCIS) is when the cells lining the milk ducts of the breast begin to become cancerous and is a very early stage of breast cancer. If a breast biopsy is reported as “ductal carcinoma in situ,” it means that some cells in the breast ducts have begun to turn into cancer cells, but the cells have not yet acquired an invasive (spreading) character. They extend only along the milk ducts and not into breast tissue. The main treatment for DCIS is surgery, in which the tumor is removed along with some normal surrounding tissue. This breast cancer surgery, also called “wide local excision” or “lumpectomy,” is a form of breast-conserving surgery (BCS). This operation is generally followed by radiotherapy and sometimes hormonal therapy (HT). In some cases, the entire breast is removed in a mastectomy operation.

Longer Hormonal Treatment Duration Linked to Benefit

In one presentation, Dr. Gillian L. Hirst of the University of California, San Francisco, discussed registry data suggesting that using hormonal therapy (HT) for longer after breast-conserving surgery (BCS) in patients with DCIS may be key to reducing the subsequent risk of cancer in the same or opposite breast.

Dr. Hirst and colleagues developed an analysis of patients with DCIS treated between 1985-2017. The registry included 1916 patients with known surgery type, radiotherapy (RT) status, receipt of HT and its duration.

Patients underwent BCS alone (401 patients), RT after BCS (572 patients), HT after BCS (152 patients), HT plus RT after BCS (252 patients), or removal of the entire breast by mastectomy (539 patients).

The median follow-up in this study was 8.2 years. Compared with BCS alone, all other treatments were associated with a reduced risk of a second cancer in a multivariable analysis.

When the researchers categorized HT use by duration, patients who received HT for more than 2 years had a significant 88% reduction in the risk of a second cancer (hazard ratio [HR] 0.12; P= 0.04).

Patients who received HT for more than 2 years after BCS had a risk reduction similar to that of patients who received RT after BCS or combined ET and RT after BCS. Dr. Hirst said that patients who received ET for less than 2 years had an event rate similar to that of patients who underwent BCS alone.

Younger Patients With DCIS May Be Inclined to Forgo Hormonal Treatment

In another presentation, Dr. Megan E. Tesch of the Dana-Farber Cancer Institute in Boston discussed data suggesting that young patients with DCIS may forgo HT even if they are eligible and it is recommended.

The data suggest that young DCIS survivors are concerned about the risk of subsequent breast cancer events, but some would prefer to try to reduce their future breast cancer risk through surgery and potentially healthy behaviors rather than taking tamoxifen.

Dr. Tesch and colleagues surveyed participants in the Young Women's Breast Cancer Study to investigate treatment decisions, cancer-preventive behaviors and fear of recurrence among young patients with DCIS.

This cohort is a prospective registry of women aged 40 or younger at diagnosis who enrolled at 13 academic and public hospitals in the United States and Canada between 2006-2016.

The current analysis includes 89 patients with DCIS who completed surveys at baseline and/or 6 months. In this group, 24.7% underwent BCS, 18% underwent unilateral mastectomy (removal of one breast), and 57.3% underwent bilateral mastectomy (removal of both breasts).

Baseline surveys showed that 65% of patients who underwent BCS, 50% of those who underwent unilateral mastectomy and 29.4% of those who underwent bilateral mastectomy were “moderately to very concerned” about breast cancer recurrence.

BCS was recommended to 46% of patients who underwent unilateral mastectomy and 76% of those who underwent bilateral mastectomy. Most patients who underwent bilateral mastectomy reported that the surgical decision was mainly their own (64%) and that they were confident about it (80% extremely confident and 18% very confident).

A total of 12 patients (13.5%) took tamoxifen, including 10 with estrogen receptor-positive, or hormone-positive, tumors.

There were 27 patients in total with estrogen receptor-positive tumors who underwent BCS or unilateral mastectomy. In this group, tamoxifen was recommended to 100% of the 10 patients who took it and 88% of the 17 who did not.

Of the patients who did not take tamoxifen, 41% said this was mainly their own decision and 29% said they made the decision together with their doctors. Data on involvement in decision-making and confidence in their decisions were missing for 24% of patients. However, 35% said they were extremely confident about their decision to forgo HT and 29% were very confident.

Some patients changed their lifestyle choices after a DCIS diagnosis. Four patients quit smoking within 1 year of diagnosis, 8% (6/72) reduced their alcohol consumption, and 73% (58/80) reported engaging in more than 150 minutes of moderate-intensity physical activity per week.

Changing the Dose and Duration of Hormonal Therapy for DCIS

Some oncologists may consider the benefits of HT worth its risks for patients with DCIS. Research from the Young Women's Breast Cancer Study cohort suggests that young women with DCIS may view the situation differently.

Their responses suggest that patients understand the importance of reducing the risk of subsequent breast cancer events and are willing to make sacrifices to reduce their risk. However, they often prefer mastectomy and exercise to breast-conserving surgery (BCS) and HT.

A review of adherence to HT suggested that fewer than half of patients with breast cancer would complete their prescribed 5-year treatment. Factors associated with this reluctance or nonadherence to HT include side effects, a low perceived risk of recurrence, extremes of age, medication costs, inadequate patient-physician communication and a lack of social support.

Recent research suggests that reducing the dose and duration of HT may improve adherence by reducing side effects.

With a reduced tamoxifen dose (5 mg) and duration (3 years), the incidence of thromboembolism (blood clots) and subsequent uterine cancer was lower than expected with the standard tamoxifen dose (20 mg/day) and duration (5 years). However, the reduced dose and duration provided a similar reduction in subsequent breast cancer risk to the standard regimen.

A real-world study of patients with noninvasive breast lesions, namely DCIS and LCIS, for whom HT was recommended found that 76% of those offered a choice selected a reduced tamoxifen regimen. Ongoing research is investigating low-intensity aromatase inhibitor regimens for chemoprevention (methods of reducing cancer risk).