Optimizing DCIS Treatment: From Surgery to Endocrine Therapy and Beyond

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• Current DCIS Treatment Approaches
• The Role of Surgery in DCIS
• Radiotherapy Decision-Making Challenges
• Endocrine Therapy for Recurrence Prevention
• Tamoxifen and Aromatase Inhibitors: Clinical Evidence
• Patient Selection and Tolerability of Hormonal Therapy
• The Importance of Biomarker Testing in DCIS
• Future Directions in DCIS Management

Current DCIS Treatment Approaches

Ductal Carcinoma In Situ (DCIS) represents the earliest, non-invasive form of breast cancer, confined to the milk ducts. Dr. Jack Cuzick, MD, describes the treatment landscape for this localized breast cancer as "quite complex." The standard approach for most women involves breast-conserving therapy, which typically combines a surgical procedure with radiation therapy. This combination aims to eradicate the abnormal cells while preserving the breast.

Despite these treatments, a minority of patients experience a recurrence. However, Dr. Jack Cuzick, MD, emphasizes a critical point: the vast majority of women diagnosed with DCIS never have a recurrence. This fact has led to significant debate within the oncology community about whether current treatment protocols might be excessive for many patients, sparking research into more personalized and de-escalated strategies.

The Role of Surgery in DCIS

Surgery remains a cornerstone of DCIS management. Dr. Jack Cuzick, MD, states his personal view that a lumpectomy to remove the bulk of the tumor is "likely to be very effective." Surgical techniques have advanced considerably over the past decade, leading to improved outcomes for patients.

A key factor in this improvement is the heightened attention surgeons now pay to achieving clear surgical resection margins. This means ensuring that no cancerous cells are found at the edges of the removed tissue. Dr. Jack Cuzick, MD, notes that this focus on obtaining clear margins has had a "major impact," contributing to the very low local recurrence rates seen with DCIS today.

Radiotherapy Decision-Making Challenges

One of the most pressing questions in DCIS care is determining which patients truly benefit from radiotherapy. Dr. Jack Cuzick, MD, identifies this as a "bigger challenge," suggesting that far too many women currently receive this treatment. He cites usage rates of almost 100% in the United States and over 70% in the United Kingdom.

Dr. Cuzick argues that "probably many of these women don't need radiotherapy." The central challenge for oncologists is to develop better tools and criteria to accurately identify the subset of patients with DCIS who are at a high enough risk of recurrence to justify the side effects and costs associated with radiation treatment, thereby sparing low-risk patients from unnecessary therapy.

Endocrine Therapy for Recurrence Prevention

Beyond surgery and radiation, endocrine (hormonal) therapy plays a crucial role in managing DCIS and preventing new cancers. Dr. Jack Cuzick, MD, has extensive research experience in this area, both for invasive cancers and in the prevention setting. Medications like tamoxifen and aromatase inhibitors (letrozole, anastrozole) can significantly reduce recurrence rates.

Dr. Jack Cuzick, MD, explains that the benefit of these medications extends beyond preventing a recurrence in the same breast. For the majority of women with DCIS, who are at a very high risk of developing new tumors in the opposite breast, endocrine therapy acts as a preventive measure for entirely new breast cancers, making it a powerful tool in comprehensive care.

Tamoxifen and Aromatase Inhibitors: Clinical Evidence

The efficacy of endocrine therapy is supported by clinical trial data. Dr. Jack Cuzick, MD, references two major clinical trials investigating tamoxifen for DCIS. The first trial demonstrated a clear benefit, reducing the risk of both local recurrence and contralateral (opposite breast) tumors.

Dr. Cuzick's own clinical trial showed a more nuanced result. While it did not show a strong positive effect for preventing local DCIS recurrence, it confirmed that tamoxifen has a significant effect on preventing new tumors in the opposite breast. This solidifies the role of these medications as a preventive strategy, even if their impact on local recurrence alone can vary.

Patient Selection and Tolerability of Hormonal Therapy

The decision to prescribe endocrine therapy is not automatic and requires careful patient consultation. Dr. Jack Cuzick, MD, acknowledges that some women experience side effects from tamoxifen and other hormonal medications, making them difficult to tolerate.

For patients who struggle with these side effects, Dr. Jack Cuzick, MD, states that "it's not unreasonable not to take hormonal therapy for DCIS." This highlights the importance of a shared decision-making process between the patient and their oncologist, weighing the potential benefits of risk reduction against the impact on the patient's quality of life.

The Importance of Biomarker Testing in DCIS

Effective use of endocrine therapy is entirely dependent on the biological characteristics of the DCIS. Dr. Jack Cuzick, MD, is clear that these treatments are "almost certainly only appropriate for estrogen receptor-positive DCIS." This means the cancer cells must have receptors that use estrogen to grow.

He points out a historical issue: until recently, hormone receptor status was not routinely measured in DCIS specimens in many places. Furthermore, other biomarkers are important; for example, Dr. Jack Cuzick, MD, notes that 40% of DCIS tumors are HER2 positive. Testing for these markers is critical for determining the most effective, personalized treatment plan and how much therapy is needed.

Future Directions in DCIS Management

The management of Ductal Carcinoma In Situ is moving towards greater personalization. The interview with Dr. Jack Cuzick, MD, conducted by Dr. Anton Titov, MD, underscores that nearly every aspect of DCIS therapy is being questioned and refined. The goal is to move away from a one-size-fits-all model.

Future progress will rely on robust biomarker research to better stratify risk, the development of decision-making tools to guide radiotherapy use, and continued patient education on the benefits and tolerability of preventive endocrine therapy. This personalized approach ensures patients receive the most effective treatment while minimizing unnecessary interventions and side effects.

Full Transcript

Dr. Anton Titov, MD: Let's start with breast cancer. Ductal Carcinoma In Situ, DCIS, is the earliest and localized form of breast cancer. But the decision-making on treatment is important.

Dr. Anton Titov, MD: How to best treat localized breast cancer?

Dr. Jack Cuzick, MD: It is quite complex. Most women with DCIS have local breast-conserving therapy and radiation therapy. A minority of women with DCIS have recurrence despite those treatments. But the vast majority of patients with Ductal Carcinoma In Situ never recur. So DCIS treatment might be excessive.

Dr. Anton Titov, MD: You have done major work in treatment decision-making in DCIS. What could you tell about your work? What the results of DCIS therapy have you obtained?

Dr. Jack Cuzick, MD: It's certainly true that the treatment of DCIS is a major challenge. There's really nothing in DCIS therapy that isn't being questioned at the moment. Some people are even concerned that it may not be necessary to do any surgery.

My personal view is that the lumpectomy to take out the bulk of the tumor is likely to be very effective. Surgery for DCIS has improved over the last decade or so. Surgeons take much greater attention to getting clear surgical resection margins. That had a major impact on the very low local recurrence rate. We see very little recurrence with DCIS.

One of the bigger challenges is this: who needs radiotherapy? At the moment, there probably are far too many women getting radiotherapy for DCIS. It's almost 100% in the United States and over 70% in the United Kingdom. Probably many of these women don't need radiotherapy. It's our challenge to figure out who does need radiotherapy for DCIS.

Our work has focused on endocrine therapy for DCIS. We have done work both for invasive cancers and also in the prevention setting. We do clinical trials using tamoxifen or other aromatase inhibitors, like letrozole or anastrozole. They could actually reduce recurrence rates in DCIS.

The effects of tamoxifen are real. There have been two clinical trials looking at the effects of tamoxifen in DCIS. One clinical trial showed a clear benefit in local and contralateral breast cancer tumors. In our own clinical trial, results were not so positive for local recurrence for DCIS. It did show an effect on contralateral tumors.

So I think radiotherapy is still a bit of an option. But for women that tolerated endocrine therapy well, aromatase inhibitors and tamoxifen prevent recurrences. That's the majority of women with DCIS. These women are at very high risk of new breast tumors in the opposite breast. So it's not only recurrence; it's actually preventive therapy for new breast cancers.

The effects in DCIS prevention are not so striking as they are with invasive cancer. Some women do have side effects from hormonal therapy for DCIS. Some women have difficulty tolerating tamoxifen and other hormonal medications. For such patients, it's not unreasonable not to take hormonal therapy for DCIS.

Aromatase inhibitors and tamoxifen are almost certainly only appropriate for estrogen receptor-positive DCIS. Until recently, in many places, receptor status in DCIS is not routinely measured. So there are a range of issues there.

Other issues relate to other markers. 40% of DCIS tumors are HER2 positive. That may be important as well for determining how much hormonal therapy should be given.