What factors do you prioritize when deciding whether to refer for neoadjuvant chemotherapy versus proceeding directly to surgery?

Highlights

• For stage II/III triple-negative or HER2-positive breast cancer, neoadjuvant chemotherapy is the established standard of care before any surgery.
• A primary goal of neoadjuvant therapy is to shrink tumors, potentially allowing for less extensive surgery and avoiding axillary lymph node dissection.
• Assessing tumor response to neoadjuvant treatment provides critical prognostic data to help guide and personalize subsequent therapy choices after surgery.
• For hormone-positive cancers, upfront surgery is common, but neoadjuvant chemotherapy is considered for a high nodal burden to improve surgical outcomes.
• Even a short course of neoadjuvant endocrine therapy can gauge tumor response by checking for a drop in the Ki-67 proliferation rate.

Article

The Neoadjuvant Decision: A Subtype-Driven, Multidisciplinary Approach

The determination of whether to pursue neoadjuvant therapy or proceed directly to surgery for breast cancer patients is a complex, evolving decision centered on a multidisciplinary discussion. Dr. Karen Goodwin, a breast surgical oncologist, emphasizes that while surgeons have a significant voice, the medical oncology team's guidance is paramount. The core of the deliberation for patients with Stage II or III disease involves assessing whether preoperative treatment can optimize outcomes. This decision is not merely about chemotherapy; as Dr. Goodwin notes, it can include neoadjuvant endocrine therapy, underscoring a personalized approach aimed at providing treatment that is "not too much, but... not not enough."

"it's really about personalizing their treatment... so that they don't get too much, but they don't get not enough." Dr. Karen Goodwin

Standard of Care for Aggressive Subtypes

For patients with Stage II or III triple-negative (TNBC) or HER2-positive (HER2+) breast cancer, there is a clear consensus. Dr. Ashley Davenport, a medical oncologist, states that neoadjuvant chemotherapy—supplemented with immunotherapy or HER2-directed therapy, respectively—is the current standard of care. Dr. Anastasia Martynova, also a medical oncologist, provides a specific clinical threshold, noting that for these aggressive subtypes, any tumor exceeding 2 cm should be considered for neoadjuvant chemotherapy. The rationale is twofold: to improve surgical outcomes and to gain crucial prognostic information. Dr. Martynova explains that observing the response to systemic therapy allows clinicians to adjust adjuvant treatment accordingly, an opportunity that is forfeited with an surgery-first approach.

"The reason for neoadjuvant chemotherapy is not only to improve surgical outcome, but also for prognostication because we can switch the adjuvant therapy depending on the response." Dr. Anastasia Martynova

The Nuanced Landscape of HR-Positive Disease

The decision-making process is more intricate for patients with hormone receptor-positive (HR+), HER2-negative breast cancer. Dr. Davenport observes that the vast majority of these cases, particularly in postmenopausal women, will likely go directly to surgery. However, a critical exception arises in the presence of a significant nodal burden. Both Dr. Davenport and Dr. Martynova highlight that concern for extensive lymph node involvement (e.g., >4 nodes) is a primary reason to consider neoadjuvant chemotherapy in an HR+ patient. The goal in this context is often the de-escalation of axillary surgery to reduce the risk of lymphedema. Dr. Martynova adds the important caveat that most HR+ tumors do not respond robustly to chemotherapy, which makes the risk-benefit discussion particularly important.

"The question is more complex for hormone positive patients." Dr. Ashley Davenport

The Twin Goals: Surgical De-escalation and Prognostication

Beyond specific subtypes, the fundamental drivers for considering neoadjuvant therapy are the potential for surgical de-escalation and the ability to assess treatment response in vivo. Dr. Goodwin notes that a key question is whether preoperative treatment can facilitate a less invasive operation, such as converting a planned mastectomy to a lumpectomy or an extensive axillary dissection to a sentinel lymph node biopsy. This point is echoed by Dr. Martynova, who links it directly to improved surgical outcomes. Equally important is the prognostic value. As Dr. Goodwin articulates, observing the pathologic response to treatment provides confidence in the chosen regimen or, conversely, signals the need to switch to a different therapy in the adjuvant setting. This real-time biological feedback is invaluable for personalizing a patient's long-term treatment plan. This can even apply to short-course neoadjuvant endocrine therapy, where a drop in the Ki-67 proliferation index can confirm endocrine sensitivity and guide further systemic treatment choices.