Siow ZR, De Boer RH, Lindeman GJ, Mann GB. Spotlight on the utility of the Oncotype DX® breast cancer assay. Int J Womens Health. 2018 Feb 21;10:89-100.
Summary: Genomic assays such as Oncotype DX have changed the landscape for the treatment of ER-positive early breast cancer. In a USA-based study, there has been a 13% decline in the use of adjuvant chemotherapy in 2006–2008, which has been largely attributed to the introduction of the Oncotype DX in 2004.78 While the Oncotype DX is expensive, the potential cost savings from chemotherapy avoidance and reduced exposure to the side effects of cytotoxic therapy appear to be cost-effective in most jurisdictions. The development and eventual validation of other genomic assays could potentially reduce test costs. While Oncotype DX is currently well validated in the node-negative population, its optimal use remains to be defined for cohorts of patients with intermediate-risk RS, as well as for patients with lymph node-positive disease. Results from the prospective TAILORx and RxPONDER trials will help shed light on these questions.
Cavalcante FP, Millen EC, Zerwes FP, Novita GG. Role of Axillary Surgery After Neoadjuvant Chemotherapy. JCO Glob Oncol. 2020 Feb;6:238-241.
“In a US study, associating selective localization and removal of clipped nodes with SLN dissection, known as targeted axillary dissection, reduced false-negative rates to approximately 2% compared with 4% with removal of the clipped lymph node alone.  However, patients are required to undergo two procedures: placement of the clip before systemic treatment and marking it to identify the lymph node during surgery. A retrospective analysis showed that in patients with clipped lymph nodes who were referred for preoperative marking, the clip failed to be identified in 20% of those patients, even when computed tomography was used, with the additional risk of the clip not being removed during surgery.  Therefore, the use of clips is controversial, because it is sometimes impossible to remove the clip alone. Despite the association between the number of lymph nodes and false-negative rates, there are still no convincing data regarding clinical outcome.”
Caudle AS, Yang WT, Krishnamurthy S, et al. Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection. J Clin Oncol. 2016 Apr 1;34(10):1072-8.
Results: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7).
Conclusion: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.
One discussion this week included nodal management after neoadjuvant chemotherapy (NAC).
Reference: Pilewskie M and Morrow M. Axillary nodal management following neoadjuvant chemotherapy. JAMA Oncology. 2017 Apr 1;3(4):549-555.
Summary: The increasing use of NAC has raised questions about the optimal approach to the axilla, including accuracy and timing of sentinel lymph node biopsy (SLNB) in patients who are clinically node negative (cN0) at presentation, use of NAC to avoid axillary lymph node dissection (ALND) in patients presenting with node-positive disease, and the relative importance of pre-and post-NAC stage in predicting the risk of locoregional recurrence (LRR).
The decrease in nodal metastases in cN0 patients undergoing post-NAC axillary staging and the increasing rates of pCR in the breast in patients treated with current chemotherapy regimens led to the study of SLNB among patients presenting with cN+ disease. Table 3 (below) summarizes data from three prospective, multi-institutional trials assessing the accuracy of SLNB after NAC among node-positive patients.
The authors conclude: NAC reduces the need for ALND, and SLNB is an accurate
method of determining nodal status post NAC. The demonstration that SLNB accurately stages the axilla after NAC regardless of the presenting nodal stage (cN0, cN1) provides an important rationale for the use of NAC for axillary downstaging in patients who are candidates for breast-conserving surgery at presentation or who desire mastectomy. SLN identification rates and FNRs in those who are cN0 are similar to those seen with initial SLN surgery, and nodal recurrence after a negative SLNB is uncommon.
Additional Reading: Boughey JC, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-1461. doi:10.1001/jama.2013.278932.
One discussion last week included Dr. Wood’s ONCOTYPE IQ for DICS, Trial E5194.
Reference: Solin LJ, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 study. Journal of Clinical Oncology. 2015 Nov 20;33(33):3938-3944. doi: 10.1200/JCO.2015.60.8588
Summary: The Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (ECOG-ACRIN; formerly the Eastern Cooperative Oncology Group) Cancer Research Group E5194 study (a nonrandomized clinical trial) prospectively enrolled patients for whom surgical excision alone (without radiation) was thought to be a reasonable treatment option on the basis of low-risk clinical and pathologic characteristics. This report provides updated results from the ECOG-ACRIN E5194 study, including 10- and 12-year outcomes.
One discussion last week included the ACOSOG Z0011 RCT.
Reference: Giuliano AE, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized control trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.
Summary: The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course. In this follow-up study, the authors sought to determine whether the 10-year overall survival of patients with 2 or fewer sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection.
Compared with ALND, SLND alone was found to be noninferior for overall survival. The 10-year overall survival rate was 86.3% in the SLND alone group and 83.6% in the ALND group. The unadjusted HR comparing overall survival between the SLND alone group and the ALND group was 0.85 (1-sided 95% CI, 0–1.16), which did not cross the prespecified noninferiority HR margin of 1.3. The HR for overall survival adjusting for adjuvant therapy (chemotherapy, endocrine therapy, radiation, or a combination of these 3) and age for the SLND alone group compared with the ALND group was 0.93 (1-sided 95% CI, 0–1.28) (Table 2).
CONCLUSION: In this randomized clinical trial including 856 women, after median follow-up of 9.3 years, overall survival for patients treated with sentinel lymph node dissection alone was not inferior to those treated with completion axillary lymph node dissection (86.3% vs 83.6%, respectively; noninferiority hazard ratio margin of 1.3). These findings do not support the use of axillary lymph node dissection when 2 or fewer metastases are found with sentinel lymph node sampling in women with cT1-2M0 breast cancer.
One discussion this week included the composition of post-surgical seroma fluid.
Reference: Valeta-Magara A, et al. Pro-oncogenic cytokines and growth factors are differently expressed in the post-surgical wound fluid from malignant compared to benign breast lesions. SpringerPlus. 2015 Sep 5;4:483. doi:10.1186/s40064-015-1260-8.
Summary: Post-operative accumulation of seroma in the surgical cavity following breast cancer surgery varies in incidence from 2.5 to 51 % of patients. Analysis of seroma has shown that it is an inflammatory exudate, classically seen in the first phase of wound repair. Given that seroma is derived from the wound-healing response of tumor-adjacent stroma, Valeta-Magara et al (2015) explored “whether seroma derived from the excision of benign tumors differs from that of malignant tumors, as malignant and benign tumors may activate or influence the adjacent stroma and infiltrating immune cells differently.”
Post-surgical seroma fluids from 59 patients who had undergone either lumpectomy or mastectomy breast surgery were collected at week 1 or 2 post-surgery by percutaneous aspiration.
It was found that surgical cavity seroma from breast cancer patients has ahigher expression of certain tumorpromoting cytokines, including GRO, ENA-78/CXCL5 and TIMP-2, and lower expression of tumor-inhibiting cytokines IGFBP-1, IL-16, IFN-γ, IL-3 and FGF-9, when compared to seroma from non-cancer patients (p.2). Patients with high body mass index also had higher levels of leptin regardless of malignancy.
In conclusion, breast post-surgical tumor cavity contains factors that are pro-inflammatory regardless of malignant or benign disease, but in malignant disease there is significant enrichment of additional pro-oncogenic chemokines, cytokines and growth factors, and reduction in tumor-inhibiting factors. These results are consistent with tumor conditioning of surrounding normal stromal tissue and creation of a pro-oncogenic environment that persists long after surgical removal of the tumor.
The authors also note that a differential expression of the eight factors between benign and malignant seroma fluid offers research hypotheses to be explored further to determine their role in breast tumor progression, local recurrence and metastasis.