The most recent breast cancer guidelines released by the National Comprehensive Cancer Network (NCCN) continue to rate breast-conserving surgery for early-stage invasive disease as being supported by the highest-level—category 1—evidence (ie, based upon data from prospective randomized clinical trials). Several management strategies may be employed to expand the number of patients who are deemed eligible for breast-conserving surgery. These include reversal of conventional primary surgery/systemic therapy treatment sequence by delivery of neoadjuvant chemotherapy; broadened applications of lumpectomy to patients with multiple breast tumors; omission/modification of breast irradiation after lumpectomy; and newer approaches to oncoplastic breast reconstruction for lumpectomy patients.
Neoadjuvant Systemic Therapy
The benefits of neoadjuvant chemotherapy in women with unresectable breast cancer became apparent several decades ago. In this scenario neoadjuvant chemotherapy was shown to improve operability, and successfully downstaged patients from this era routinely underwent modified radical mastectomy. The neoadjuvant treatment plan also offers the following advantages[2,3]:
• It enables clinicians to monitor disease chemosensitivity, since breast tumor downstaging by neoadjuvant chemotherapy is a surrogate marker for the effectiveness of chemotherapy in sterilizing micrometastases.
• It increases the possibility of downstaging axillary disease, so that patients are more likely to be node-negative after primary chemotherapy—which then potentially increases the likelihood that axillary lymph node dissection will not be necessary. A comprehensive discussion of axillary surgical management in neoadjuvant chemotherapy is beyond the scope of this review. Many patients receiving neoadjuvant chemotherapy who present with node-positive breast cancer will require axillary lymph node dissection for definitive staging and regional control of disease. However, NCCN guidelines support the option of omitting axillary lymph node dissection in patients with needle biopsy–proven nodal disease whose axilla has been proven to be downstaged following neoadjuvant chemotherapy through a targeted axillary dissection involving dual-agent (blue dye and radiotracer) lymphatic mapping, resection of more than two sentinel nodes, and radiographic confirmation that the original biopsied/clip-marked lymph node has been removed.
• It may provide patients with an additional window of time during which they can seek genetic counseling/testing, as well as contemplate their individual preferences regarding lumpectomy vs mastectomy.
Several international studies have confirmed the safety of reversing the conventional breast cancer treatment sequence, so that chemotherapy precedes surgery (Table 1). Overall survival is the same within each study for the two randomization arms, definitively demonstrating that survival is not compromised by modest delays in performing surgery while chemotherapy is delivered preoperatively. These studies also confirm that the neoadjuvant approach increases the volume of patients who are eligible for breast-conserving surgery.
Candidates for neoadjuvant chemotherapy must be carefully vetted to ensure that all necessary cancer-related information is available to the care team prior to initiating treatment. A radio-opaque clip must be left in place within the tumor bed for subsequent lumpectomy targeting. Mammograms showing microcalcifications may be used as inherent tumor localization markers. Patients who are fortunate enough to achieve a complete clinical response but who have neither marker clips nor calcifications to identify the tumor bed must undergo mastectomy after receiving neoadjuvant chemotherapy. Patients who have diffuse microcalcifications or multiple widely spaced tumors at the time of diagnosis should be informed that they must undergo mastectomy regardless of how well they respond to neoadjuvant chemotherapy. Patients with several tumors should have multiple biopsies to completely characterize biomarker expression, since this information will determine individual eligibility for endocrine therapy and targeted therapy with anti–human epidermal growth factor receptor 2 (HER2) agents.
Breast imaging should be repeated after completion of neoadjuvant chemotherapy, to assess the patient’s response to treatment and facilitate surgical planning. Occasionally, patients will have unmasking of previously obscured microcalcifications that might influence their eligibility for lumpectomy. The standard of care at this time is for patients receiving neoadjuvant chemotherapy to routinely undergo definitive breast surgery; ongoing research and clinical trials (including the NRG Oncology trial NRG-BR005) will explore the prospect of avoiding surgery in the subset of patients appearing to be “exceptional responders”—that is, cases in which clinical evaluation, postchemotherapy core needle biopsies, and breast imaging are consistent with a complete pathologic response.
Bulky cancers that are hormone receptor (HR)-positive and HER2-negative are less likely to have a brisk response to neoadjuvant chemotherapy and are generally triaged toward primary surgery unless they are associated with biopsy-proven nodal disease or are unresectable. Neoadjuvant endocrine therapy is an alternative option for this phenotype, but clinical response tends to be relatively slow and complete pathologic responses are uncommon.[4-7] Improved eligibility for lumpectomy is therefore less well documented compared with neoadjuvant chemotherapy delivered for triple-negative breast cancer (ie, tumors that are estrogen receptor–negative, progesterone receptor–negative, and HER2–negative) or cancers that overexpress the HER2 protein.
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