Neoadjuvant Chemotherapy for Operable Breast Cancer: Individualizing Locoregional and Systemic Therapy

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Potential benefits of neoadjuvant chemotherapy for breast cancer

Classically, neoadjuvant chemotherapy (NAC) was used only for patients with locally advanced breast cancer (LABC), corresponding approximately to American Joint Commission on Cancer stage III.1 Once the success of downstaging those patients with chemotherapy was appreciated, similar strategies began to be used for patients with operable breast cancer but who were not ideal candidates for breast-conserving surgery (BCS). Initially, this approach was tested to determine whether primary or

Predicting response to neoadjuvant chemotherapy

Based on these advantages, it has been suggested that anyone with a T2 or larger tumor or clinically evident or ultrasound (US)-detected lymph node involvement at presentation is a potential candidate for NAC. A less well-defined, but perhaps more practical, guideline might be that NAC should be considered for any patient in whom it is clear that adjuvant chemotherapy would be indicated. As more is learnt about breast cancer biology, this decision will be based only partly on the anatomic

Chemotherapy versus hormonal therapy

As noted earlier, there are emerging data suggesting that certain subsets of tumors, especially among those that are ER+ and/or PR+, may not respond well or in a clinically useful way to chemotherapy. For example, in the I-SPY trial, only 5% of luminal A tumors had a pCR to chemotherapy.33 As recently reviewed, aromatase inhibitors seem to be superior to tamoxifen as neoadjuvant therapy for postmenopausal women with hormone-responsive tumors.36, 37, 38, 39, 40 Aromatase inhibitors as

Pre-therapy assessment and staging

Once the decision has been made to treat a patient with breast cancer with NAC, several studies in addition to those that are routine (mammograms, routine laboratory tests, and so forth) should be performed. Although controversial as a standard study for all breast cancers, magnetic resonance imaging (MRI) of the breasts is particularly valuable for NAC patients.44, 45, 46, 47, 48 MRI provides information about the extent of the known cancer, possible multicentric disease, axillary and internal

Optimal chemotherapy regimen

Space does not allow a detailed review of the different chemotherapy regimens that can be used in the neoadjuvant setting for operable breast cancers. A recent expert consensus panel concluded that for most patients, regimens that combine anthracycline and taxane therapy, either concurrently or sequentially, have the greatest likelihood of a good clinical and pathologic response, and that the duration of therapy should extend to 4 to 6 months.15, 53, 54, 55, 56, 57 Indeed, recent trials have

Assessing response to neoadjuvant chemotherapy

One of the more difficult tasks associated with the use of NAC for breast cancer is the assessment of the tumor response during and at the completion of treatment. Clinical examination has been used in several studies, but suffers from a lack of reproducibility, especially when different examiners are involved. The German neoadjuvant trials have depended on US examination of the breast to assess changes in tumor size more accurately.60 Recently, there has been a great deal of interest in the

Resection of the primary tumor: breast conservation versus mastectomy

It is easy to appreciate that the type of response can profoundly influence the likelihood of obtaining a negative margin with BCS and the risk of ipsilateral breast tumor recurrence (IBTR). Unfortunately, as noted earlier, there are no highly reliable clinical or radiographic methods for assessing the extent and type of response accurately. A scoring system, based on clinical nodal stage, residual pathologic tumor size, lymphovascular invasion, and multifocal pattern of residual cancer has

Management of regional lymph nodes in patients treated with NCT

Although sentinel lymph node biopsy (SLNB) has largely replaced complete axillary node dissection for women with clinically negative lymph nodes undergoing primary surgery for breast cancer, the role and timing of SLNB in women who are treated with primary systemic therapy is highly controversial. Widely consulted guidelines suggest that NAC is a contraindication to the use of SLNB for staging of the regional lymph nodes.76, 77 Some have advocated pretreatment SLNB for patients with clinically

Postmastectomy regional/chest wall irradiation after neoadjuvant chemotherapy

One remaining concern about these patients is whether to treat with regional and/or chest wall irradiation. Data from NSABP trials and from MD Anderson indicate a high risk for locoregional recurrence in patients with residual cancer after chemotherapy who do not receive regional irradiation.98, 99, 100 Conversely, patients who were not stage IIIB or C and who have negative nodes after chemotherapy seem to be at low risk for locoregional recurrence.98, 101, 102 However, until definitive data

Summary

Neoadjuvant chemotherapy has many practical advantages for women with operable breast cancer, including increased chance for breast conservation. The potential to decrease the need for ALND is promising, but controversial. Hormonal neoadjuvant therapy may be more appropriate for some women. Perhaps most importantly, correlating responses to NAC with molecular profiles has the potential to increase our understanding of breast cancer biology and accelerate progress toward optimizing and

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