Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. Here we demonstrate that ...neutrophils accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H
2O
2 and tumor secreted CCL2 is a critical mediator of optimal antimetastatic entrainment of G-CSF-stimulated neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, whereas tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.
► Tumor entrained neutrophils (TENs) accumulate in the premetastatic lung ► TENs provide antimetastatic protection by eliminating disseminated tumor cells ► Tumor-secreted factors are both required and sufficient for neutrophil entrainment ► Tumor-secreted TGF-β protects the primary tumor from neutrophil cytotoxicity
Early randomized trials of the addition of neoadjuvant chemotherapy (NACT) to the treatment regimen of patients with breast cancer failed to demonstrate an improvement in overall survival compared ...with conventional adjuvant therapy; nevertheless, the increased opportunities for breast conservation, owing to downstaging of the primary tumour, and enthusiasm regarding the potential to tailor systemic therapy based on responses observed in the neoadjuvant setting, resulted in the adoption of this approach as a useful clinical tool. That the effectiveness of NACT varies by molecular subtype is becoming increasingly clear, and although the potential of tailoring adjuvant systemic therapy based on treatment response before surgery remains to be realized, the increasing rates of pathological complete response following NACT have had a considerable impact on locoregional treatment considerations. For example, NACT reduces the need for mastectomy and axillary lymph-node dissection, thus decreasing the morbidity of surgery, without compromising outcomes. However, selection of the ideal candidates for preoperative chemotherapy remains critical, and personalizing local therapy based on the degree of response is the subject of ongoing clinical trials. This article reviews the current issues surrounding surgery of the breast and axilla in patients with breast cancer receiving NACT.
The role of axillary surgery has evolved over the last three decades from routine axillary lymph node dissection (ALND) to sentinel lymph node biopsy to omission of axillary surgery altogether in ...select patients. This evolution has been achieved through the design and conduct of multiple clinical trials demonstrating that ALND does not impact survival and is not necessary for local control in patients with early-stage breast cancer and limited nodal involvement. Importantly, this practice-changing shift mirrored the trend towards earlier stage at diagnosis and the recognition of the interplay between local and systemic therapies in maintaining local control. There are numerous clinical scenarios today in which axillary staging can be safely avoided, including (1) DCIS treated with lumpectomy, (2) at the time of contralateral prophylactic mastectomy, and (3) in elderly patients with early-stage, HR+/HER2-clinically node-negative (cN0) disease. Ongoing clinical trials seek to expand the cohorts in which surgical nodal staging can be omitted. These populations include a broader range of early-stage, cN0 patients undergoing upfront surgery, as seen in the SOUND, INSEMA, BOOG 2013–08, SOAPET and NAUTILUS trials. Omission of axillary surgery in cN0 patients with HER2+ or triple-negative disease treated with neoadjuvant chemotherapy is also being tested in the ASICS and EUBREAST-01 trials. Continued advances in imaging and the growing role of genomic assays in selecting patients for systemic therapy are likely to further minimize the need for axillary surgery; thereby further reducing the morbidity of local therapy for women with breast cancer.
To determine whether increasing rates of contralateral prophylactic mastectomy (CPM) are due to recognition of risk factors for contralateral breast cancer (CBC) or treatment factors related to the ...index lesion.
From 1997 to 2005, 2,965 patients with stage 0 to III primary unilateral breast cancer underwent mastectomy at Memorial Sloan-Kettering Cancer Center. Patients who did and did not undergo CPM within 1 year of treatment for their index cancer were compared to identify independent predictors of CPM.
The rate of CPM was 13.8% (n = 407), increasing from 6.7% in 1997 to 24.2% in 2005 (P < .0001). Patients with BRCA mutations or prior mantle radiation (n = 52) accounted for 13% of those having CPM. The rate of CPM by surgeon varied from 1% to 26%. Multivariate logistic regression adjusting for surgeon-identified white race (odds ratio OR = 3.3), immediate reconstruction (OR = 3.3), family history of breast cancer (OR = 2.9), magnetic resonance imaging (MRI) at diagnosis (OR = 2.8), age younger than 50 years (OR = 2.2), noninvasive histology (OR = 1.8), and prior attempt at breast conversation (OR = 1.7) to be independent predictors of CPM.
These data suggest that increasing use of CPM is not associated with increased recognition of patients at high risk for CBC. Treatment factors, such as immediate reconstruction, preoperative MRI, and unsuccessful attempts at breast conservation, are associated with increased rates of CPM. Efforts to optimize breast conservation, minimize unnecessary tests, and improve patient education about the low risk of CBC may help to curb this trend.
This review discusses the contemporary surgical management of the axilla in patients with breast cancer. Surgical paradigms are highlighted by clinical nodal status at presentation and treatment ...approach, including upfront surgery and neoadjuvant systemic therapy settings. This review focuses on the increasing opportunities for de-escalating the extent of axillary surgery in the era of sentinel lymph node biopsy, while also reviewing the remaining indications for axillary clearance with axillary lymph node dissection.
With new investigations and clinical trials in breast oncology reported every year, it is critical that surgeons be aware of advances and insights into the evolving care paradigms and treatments ...available to their patients. This article highlights five publications found to be particularly impactful this past year. These articles report on efforts to select the minimal effective dose of tamoxifen for prevention, to challenge the existing age-based screening guidelines as they relate to race and ethnicity, to refine axillary management treatment standards, to optimize systemic therapy in multidisciplinary care settings, and to reduce the burden of breast cancer-related lymphedema after treatment. Taken together, these efforts have an impact on all facets of the continuum of care from prevention and screening through treatment and survivorship.
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