Improvements in Personalized Medicine Allow for Greater Exploration of Treatment De-escalation in Breast Cancer

Advancements in technology and drug development have allowed for more targeted therapeutic delivery across breast cancer subtypes, thereby reducing the risks associated with treatment de-escalation for specific patient subgroups and potentially improving these patients’ quality of life, according to Suzanne B. Coopey, MD, FACS.

“We’ve seen improvements in technology, innovative devices, and now we’re better able to localize breast cancers for removal. We’re [also] able to deliver more targeted radiation therapies,” Coopey said following an OncLive^® State of the Science Summit™ on breast cancer, which she cochaired. “This has allowed for safe de-escalation of many of the treatments that we once considered the standard of care.”

In the interview with OncLive^®, Coopey highlighted key topics from the meeting, including the de-escalation of axillary lymph node surgery, shifts in the use of radiation oncology, and changes in the treatment paradigm for HER2-positive disease. Coopey also highlighted the importance of biomarker testing in triple-negative breast cancer (TNBC) and the role of oral selective estrogen receptor degraders (SERDs) in endocrine receptor (ER)–positive, HER2-negative breast cancer.

Coopey is a surgical oncologist, director of the Wexford Breast Program and the co-strategy and growth officer for the Allegheny Health Network (AHN) Breast Cancer Program, AHN Cancer Institute in Wexford, Pennsylvania.

OncLive: Could you briefly discuss the benefits seen with the de-escalation of axillary surgery in patients with breast cancer?

Coopey: The number one benefit of de-escalation of axillary surgery is reducing the risk of patients developing arm lymphedema postoperatively. That’s the big thing that patients fear. Some patients can also develop things like chronic pain, chronic fluid collections, problems with range of motion [in their] shoulder, and axillary web syndrome after axillary surgery. These are all things that we’d like to try to avoid.

In what scenarios should axillary reverse mapping and primary lymphovenous bypass be utilized?

Reverse mapping is not a new technique. It’s been around for about 15 years, but it has not been widely adopted. The surgeons that use it routinely feel like it could be beneficial for any patients that have any axillary lymph nodes removed. [However], most surgeons are using it a bit more selectively, especially in patients that are having axillary lymph node dissection [ALND]. Because if there are some blue [stained] lymphatics that you can see draining from the arm and they happen to be cut during the surgery, having a plastic microsurgeon available, or being trained yourself to perform [the Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) technique] can help patients to avoid postoperative arm lymphedema.

Could you expand on current recommendations for the de-escalation or omission of ALND?

We should all feel comfortable following the Choosing Wisely campaign, which recommends not routinely performing sentinel lymph node biopsy [SLNB] in women that are age 70 and older if they have early-stage ER-positive, HER2-negative breast cancer. We should [also] be omitting ALND for patients that only have 1 or 2 positive sentinel nodes if they meet the criteria [from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial (NCT00003855)]. For patients that convert from node positive to node negative after neoadjuvant chemotherapy, we should also consider omitting ALND. There are a lot of categories of patients [in which] you can either omit axillary surgery entirely or [de-escalate] from dissection to SLNB alone.

Based on the presentation given by your cochair, Christie J. Hilton, DO, of AHN, how has the use of T-DXd evolved in HER2-positive metastatic breast cancer?

Dr Hilton emphasized that T-DXd has now become [a standard] second-line therapy for [patients with] metastatic HER2-positive breast cancer after trials like the [phase 3 DESTINY-Breast03 study (NCT03529110)] showed a significant improvement in progression-free survival [PFS] compared with ado-trastuzumab emtansine [T-DM1; Kadcyla]. Now, T-DXd is the preferred second-line treatment for metastatic HER2-positive breast cancer treatment after the first line, which is trastuzumab [Herceptin], pertuzumab [Perjeta], and a taxane.

Which key trials have informed efforts to de-escalate chemotherapy use in early-stage HER2-positive breast cancer, per the presentation given by Gurleen Pasricha, MD, of Meadville Medical Center?

Dr Pasricha focused on patients with early-stage HER2-positive breast cancer and highlighted studies where we [may be able to] de-escalate and use less chemotherapy. The first trial she talked about was the [phase 2] APT trial [NCT00542451], which now has 10-year follow-up [data]. It showed that patients who have stage I node-negative HER2-positive breast cancer can be safely treated with [adjuvant] paclitaxel and trastuzumab and [have a] very low risk of recurrence without using additional chemotherapy agents. She also talked about the [phase 3] APHINITY trial [NCT01358877], [which was] also in early-stage, node-negative, HER2-positive breast cancer. [In this trial] pertuzumab added to trastuzumab did not improve the already excellent [overall survival] outcomes seen with [chemotherapy and] anti-HER2 therapy with trastuzumab, so pertuzumab was not needed. The last trial she looked at was the [phase 3] KATHERINE trial [NCT01772472], which specifically looked at patients that had residual cancer in the breast or the lymph nodes after neoadjuvant chemotherapy for HER2-positive disease. This [trial] showed that patients had improved outcomes with T-DM1 compared with [trastuzumab]. Now patients with residual disease are being recommended maintenance therapy with T-DM1.

How could novel oral SERDs fill an important niche in the management of ER-positive, HER2-negative breast cancer, according to Diane M. Buchbarker, MD, of AHN?

Dr Buchbarker was excited about some of the new trial data coming out with these new oral SERDs. Unlike the previous SERDs and [selective estrogen receptor modulators (SERMs)], the new oral SERDs appear to be effective even in [patients with] ESR1 mutations. [Their use in this space] would provide an additional treatment [option] for patients that are progressing on traditional therapies.

What did Sarah M. Miller, DO, of AHN, emphasize about the use of biomarker testing in TNBC?

It is extremely important to test patients with TNBC for BRCA gene mutations because this can have implications [for] which chemotherapy agents they receive and what they’re going to respond to. Also, the importance of PD-L1 testing to help guide treatment decisions for patients that have metastatic TNBC [should be noted].

What radiation oncology updates shared by Colin E. Champ, MD, of AHN, are most important to know from the perspective of a surgical or medical oncologist?

Dr Champ highlighted that hypofractionated whole breast irradiation [WBI] with a concurrent boost of 40 Gy [in] 15 fractions was not found to be inferior to the standard WBI with a sequential boost of 50 Gy [in] 25 fractions. Many patients can now safely have 15 fractions of WBI rather than 25 fractions, or 10 fewer treatments. [This is] much more tolerable for patients and less disruptive to their schedules. The other thing that he focused on was accelerated partial breast irradiation [APBI] as an alternative to WBI in patients [with early-stage breast cancer] who are node negative. [This was] based on 10-year follow-up data from the [phase 3] FLORENCE trial [NCT02104895] showing that [APBI using intensity-modulated radiation therapy (IMRT)] was very effective and not inferior to WBI [in this population].

What ongoing investigations in the breast cancer space are you excited about at AHN?

Overall, breast cancer care is [becoming] more targeted and more individualized. Two of the trials that we’re participating in are the CompassHER2-pCR trial [NCT04266249] and the DESTINY-Breast05 [NCT04622319] trial. CompassHER2-pCR is a phase 2 trial looking at [the use of] preoperative trastuzumab with pertuzumab plus a [taxane], [followed by] postoperative trastuzumab and pertuzumab in patients who [achieve] a complete pathologic response [pCR]. [It’s] mostly looking to see if we can give [these patients] less chemotherapy and more targeted therapy, and if that would be an effective way to treat them. DESTINY-Breast05 is a phase 3, multicenter, randomized study looking at T-DXd vs T-DM1 in patients who have high-risk HER2-positive [breast cancer with] residual invasive disease in their breast or lymph nodes following neoadjuvant therapy. [The trial aims] to see which [agent is] more effective [at improving] PFS.