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15 March 2020

Ductal carcinoma in-situ, also known as DCIS or stage 0 breast cancer, is traditionally treated with surgical excision (lumpectomy or mastectomy). Treatment may also include radiation therapy, as well as endocrine therapy (tamoxifen or an aromatase inhibitor) if the disease is estrogen receptor positive (ER+).

For invasive cancer, we sometimes take a neoadjuvant approach, treating with chemotherapy or endocrine therapy prior to surgery. This has the advantage of confirming that the tumor will actually respond to treatment. In addition, in cases where the tumor does not completely resolve with treatment (based on pathology assessment of the tissue that is removed), additional chemotherapy or targeted treatments may be recommended.

We have not traditionally used a neoadjuvant approach for DCIS. While invasive cancers may shrink in response to treatment, it is unclear if that reliably happens with DCIS. A study recently published used letrozole (Femara – an aromatase inhibitor) in patients with ER+ DCIS. Patients were treated for 6 months, had MRIs at baseline, 3 and 6 months, and then underwent surgery. The size of abnormality on MRI (which often, but not always correlates with the amount of disease) was measured, and ER, PR (progesterone receptor) and Ki67 (a measure of cellular proliferative activity) was assessed on the pre-treatment needle biopsy and on the surgical specimen. 79 patients were enrolled, 70 completed 6 months of letrozole, and MRI data for all 3 time points was available for 67 patients.

The study found that:

  • Median volume of disease as measured by MRI declined by 0.8cm 
  • ER and PR H-scores decreased by a median of 15 and 85 points, respectively
  • Ki67 decreased by a median of 6.3%

Of the 59 patients who underwent surgery, findings included:

  • Persistence of residual disease in 50 patients (85%)
  • Invasive cancer in 6 patients (10%)
  • No residual DCIS and no invasive cancer found in 9 patients (15%)

As mentioned above, the finding of residual disease is not unexpected. DCIS does not often resolve after neoadjuvant therapy, and endocrine therapy works very slowly. In addition, several patients were found to have invasive cancer – the authors suspect that most likely this was not picked up on the initial biopsy as we know the “upstaging” rate for DCIS at surgery can approach 25%. However, despite these limitations, the finding of decreased volume of disease by MRI and changes in biomarkers (ER, PR and Ki67) indicate treatment response and suggest that extended neoadjuvant endocrine therapy may eventually play a role in the treatment of ER+ DCIS and may possible replace surgery in selected patients. This was a relatively small Phase II trial, so more study certainly is needed. 

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

26 December 2016

Approximately 75% of breast cancers express the estrogen receptor – we term these breast cancers ER positive (ER+) or hormone-sensitive. Endocrine therapy refers to using medications to exploit this cancer cell property. Tamoxifen is used in premenopausal women and it blocks the estrogen receptor. In post-menopausal women, aromatase inhibitors (AI) are used which prevent estrogen from being produced (primarily in the fat cells after menopause).

In June, a study was presented which suggested that 10 years of endocrine therapy in post-menopausal women might be superior to 5 years of treatment, which had been the standard. The study noted that disease free survival was improved and development of new breast cancers were reduced in the extended therapy patients, but there were more side effects. A conclusion was that extended therapy might be appropriate for higher risk patients – those who based on certain tumor factors we suspect might have a higher risk of recurrence. A challenge has been that we do not have good tests to tell us with certainty which patients will truly benefit from a longer course of therapy.

At the 2016 San Antonio Breast Cancer Symposium, 3 studies were presented which addressed the issue of extended endocrine therapy in post-menopausal women. In all 3 studies, extended endocrine therapy with an AI did not improve disease free survival, in contrast to the study presented in June.  A lack of survival benefit does not mean that extended therapy is not worthwhile, as noted in this ASCO Post article, and one of the studies did show improvements in distant metastases and contralateral (other side) breast cancers. Dr. Michael Gnant, who discussed the studies at the meeting, noted that “The trials did not reach the necessary statistical levels to demonstrate a clear benefit for aromatase inhibition extension. Extending aromatase inhibitor therapy may be a good idea for many patients after 2 to 5 years of tamoxifen, but after initial treatment with an aromatase inhibitor, the benefits and risks must be carefully balanced on an individual basis. We are going to need the ‘art of medicine’ here.”

While ER+ breast cancers tend to be “better behaved”, we know that these patients are at risk for relapse many years after initial treatment. This knowledge has to be balanced with the real side effects women experience from taking the medications. Common side effects of the AIs include joint and bone pains, vaginal dryness, hot flashes, and bone loss. Deciding whether or not to continue on the medications in the setting of significant side effects is also difficult for patients, who then have concerns about “not doing enough” to reduce the risk of cancer recurrence. More research is needed to develop both tests to help predict which patients will actually benefit from extended therapy, and treatments with fewer side effects,