Tumor Biology Drives Personalized Surgical Interventions in Breast Cancer

Shubhada Dhage, MD, FACS

In the past, surgical interventions such as radical mastectomies or complete axillary lymph node dissections were driven by the adage “more is better,” said Shubhada Dhage, MD, FACS. Now, surgeons are acknowledging that a greater understanding of tumor biology can be used to inform more personalized interventions, offering equal efficacy with less morbidity.

For example, patients with HER2-positive or triple-negative breast cancers (TNBC) are potential candidates for neoadjuvant chemotherapy, which could decrease disease burden to the point of not needing a complete axillary lymph node dissection.

Moreover, results from the phase III ACOSOG Z0011 trial demonstrated that axillary lymph node dissection did not have a significant impact on improving overall survival among women with limited sentinel lymph node involvement following lumpectomy and adjuvant therapy, further attesting to the benefit of tailored surgical strategies.

"The true biology of breast cancer is driving every portion of therapy, [which is resulting in more personalized surgical interventions]," said Dhage. "We’re personalizing medical therapy and radiation therapy. We used to consider these [approaches] in isolation. Now, we’re seeing more of an integration [of these modalities]."

In an interview during the 2019 OncLive^® State of the Science Summit™ on Breast Cancer, Dhage, assistant professor, Department of Surgery, director, Breast Surgical Services and associate director, Breast Health Program, NYU Winthrop Hospital, NYU Langone Health, discussed the role of surgery and other therapeutic modalities in breast cancer and explained the shift toward de-escalated treatments and less morbid surgical management strategies.

OncLive: What is the role of surgery in the modern treatment era?

Dhage: This is an exciting time in the era of surgery. We're seeing a complete de-escalation in therapy. We're getting much more specific and sensitive to what's important to the patient. We're changing our perspectives on radiation and surgery. Ultimately, [we’re employing these modalities] to reduce local recurrence and improve survival. As a surgeon, it’s important that we decrease the morbidity of treatment.

Could you expand on some of the surgical advances that have been made in recent years?

Many years ago, we did radical mastectomies, which were very disfiguring. Women had their entire muscle removed, as well as many of their lymph nodes. Now, we've moved into the era of nipple-sparing mastectomies. We can hide scars; sometimes you can’t even tell that a woman had surgery. This speaks to how we're transforming our approach to axillary surgery as well. It’s important that we evaluate how we do axillary surgery because this operation could result in lymphedema, nerve damage, and [other] long-term adverse events. [We have to figure out] how to reduce those events, while preventing the cancer from spreading and getting the [data] we need [to inform] adjuvant therapy.

How is neoadjuvant therapy being used right now?

Neoadjuvant therapy falls in line with this new culture of de-escalation. Now we know that if we give neoadjuvant chemotherapy to patients with a positive lymph node, they may not need to undergo a complete axillary dissection. Rather, they could have a central lymph node biopsy. If that biopsy ends up being negative, we could omit the axillary dissection altogether. That's pretty transformative.

How are surgical techniques helping to reduce the rate of false-negative sentinel lymph node biopsies and increasing patient eligibility for surgery?

In the past, when people considered delivering neoadjuvant therapy, the qualifications were quite stringent. Patients had to have a very large locally advanced breast cancer, which may have included significant axillary burden. Now, the tumor biology—not the size of the cancer—is almost as important in deciding whether to pursue neoadjuvant chemotherapy versus surgery.

[Now, we’re considering neoadjuvant therapy] in women with HER2-positive and TNBC. We’re expanding the number of people we can deliver neoadjuvant therapy to. We’re also increasing the number of patients we can evaluate for a pathologic complete response (pCR). While pCR hasn't been directly linked with improved survival, we can anecdotally say that patients who have a pCR tend to have better outcomes.

How does management of the axilla differ depending on whether a patient receives neoadjuvant chemotherapy or surgery first? The patients who will undergo surgery first tend to be estrogen receptor (ER)—positive or have a tumor that’s less than 2 cm in size and not HER2-positive or triple-negative. These patients may or may not have a mastectomy or a lumpectomy depending on whether they have disease in multiple areas of the breast or in one area of the breast. The ER-positive patients may not benefit from preoperative chemotherapy even if they have a positive lymph node. However, that’s case-dependent.

The patients who will receive neoadjuvant therapy first tend to be women with tumors that are about 2 cm or more in size, and those that are triple-negative or HER2-positive. This is because we’re trying to achieve a pCR in those patients and we know they're going to need adjuvant therapy afterward. Achieving a pCR and downstaging their cancer before surgery might translate to decreased surgical morbidity.

How has the ACOSOG Z0011 trial impacted practice?

The ACOSOG Z0011 trial was practice-changing. In the past, when we [performed] a lumpectomy in the operating room, we tried to get real-time results on the sentinel lymph node. If we saw 1 positive lymph node, we often did a complete axillary dissection. [Now we know that] if a patient has 1 or 2 positive lymph nodes, axillary burden can probably be taken care of by the adjuvant therapy that patients will receive. Moreover, these patients may not benefit from the increased morbidity of having an axillary lymph node dissection. This is a very big step for us. The question now is whether these results translate to women who have had mastectomies. That's definitely where we're headed.

What is coming down the pipeline?

[We are excited to see the results of an ongoing trial in which] investigators are evaluating the different types of ductal carcinoma in situ (DCIS) and the outcomes of DCIS to see which patients need surgery or radiation.

Many of us struggle with the term “DCIS.” We know some of those lesions are quite indolent. We also know that some patients have a more aggressive form of DCIS that will transform into invasive cancer. However, we don't have that algorithm down yet where we can safely say this is definitely an indolent lesion and that the patient doesn’t need the same therapy as someone who has a more aggressive form of DCIS.

It’s really important for surgeons to be open-minded—especially with this concept of de-escalation. As surgeons, we’ve always operated under the assumption that more is better. Now, we're seeing that less is more. A lot of times, we may be slower to take these changes on, but we have to remember that survival is key.

There is a discomfort when it comes to being OK with leaving potential cancer cells behind that will be treated by adjuvant therapy. However, it’s time for surgeons to embrace this. It's better for our patients to think in a way that’s more biologically savvy, where we're considering the tumor biology [when it comes to treatment].