Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial

PURPOSE Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. METHODS The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. RESULTS The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. CONCLUSION Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Effectiveness of Lymphedema Prevention Programs With Compression Garment After Lymphatic Node Dissection in Breast Cancer: A Randomized Controlled Clinical Trial

Background: Patients with breast cancer who undergo axillary lymph node dissection (ALND) are at risk of developing lymphedema, which can negatively impact quality of life. Lymphedema prevention programs, which primarily consist of educational content and exercise, have been shown to reduce the incidence of lymphedema. The addition of compression garments (CG) may increase the effectiveness of these programs.Aim: We aimed to determine whether adding a compression garment to a conventional lymphedema prevention program could improve treatment effectiveness.Design: Randomized clinical trial.Methods: Seventy patients who had undergone ALND for breast cancer were randomized to receive conventional preventative therapy (control arm, n = 35) consisting of a 1-hour educational session and a 12-week exercise program or the same therapy plus upper limb CGs (experimental arm, n = 35). Patients in the experimental arm were instructed to wear the CG ≥ 8 h/day for the first 3 months after surgery and 2 h/day thereafter.Results: At 2-years, the overall incidence of lymphedema in the two groups was 12.3%, with no significant differences between the conventional and experimental arms (12.5 vs. 12.1%). In the experimental arm, the incidence of lymphedema was significantly lower (p = 0.02) in patients who used the CGs daily as recommended compared to patient who did not adhere to this treatment recommendation. Neither exercise (p = 0.518) nor education alone decreased the incidence of lymphedema. Adherence decreased over time.Conclusions: The findings of this RCT show that health education, preventive exercise programs, and patient adherence to therapeutic recommendations all play an important role in preventing lymphedema.Clinical Rehabilitation Impact: Our data demonstrated that the use of a compression garment during the first 3 months after axillary node dissection may reduce the likelihood of lymphedema in high-risk patients.

Can machine learning be used to reduce overtreatment of the axilla in breast cancer? Results from a retrospective cohort study (Preprint)

BACKGROUND Patients with early breast cancer undergoing primary surgery who have low axillary nodal burden can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risk within large patient data sets, but this has not yet been trialled in the arena of axillary node management in breast cancer. OBJECTIVE To assess if machine learning techniques could be used to improve pre-operative identification of patients with low and high axillary metastatic burden. METHODS A single-centre retrospective analysis was performed on patients with breast cancer who had a preoperative axillary ultrasound, and the specificity and sensitivity of AUS were calculated. Machine learning and standard statistical methods were applied to the data to see if, when used preoperatively, they could have improved the accuracy of AUS to better discern between high and low axillary burden. RESULTS The study included 459 patients; 31% (n=142) had a positive AUS, and, among this group, 62% (n=88) had two or fewer macrometastatic nodes at ANC. When applied to the dataset, logistic regression outperformed AUS and machine learning methods with a specificity of 0.950, correctly identifying 66 patients in this group who had been incorrectly classed as having high axillary burden by AUS alone. Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS Machine learning greatly improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than two metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low burden and it is unclear if sentinel node biopsy adds value in this situation. CLINICALTRIAL n/a

Clinical Value of Size, quadrant, and Hormonal Status in Predicting Axillary Node Metastasis in Early Clinico-Radiologically Negative Indian Breast Cancer- A Hospital Based Prospective Observational Study

Background: Sentinel lymph node biopsy (SLNB) is standard of care in clinico- radiologically negative axilla in early breast cancer case. It’s an oncologically safe alternative to Axillary lymph node dissection (ALND), however factors predicting sentinel node metastasis in Indian population is lacking. Methods: A prospective observational study which recruited 80 patients with breast cancer who underwent SLNB with or without ALND, with evaluation of predictive factors including size, type and quadrant , hormonal status of breast this characteristics were prospectively analyzed to predict the axillary metastasis and need of SLNB . Result: Mean age of the patients included in our study was 52.4 years. On univariate analysis, size (p<0.013), upper outer quadrant (UOQ) (p<0.038), central quadrant (CQ) (0.07) were significantly associated with axillary node metastasis in T2 tumors. While on multivariate analysis, UOQ (P<0.009), CQ (p<0.02) metastasis were associated with axillary node metastasis in T2 tumors. Overall sensitivity, specificity, positive predictive valve (PPV) and negative predictive valve (NPV) of SLNB in predicting axillary node status was 77.59%, 100%, 100% and 62.86% respectively. The overall accuracy was 83.7%. Conclusion: Upper outer quadrant, central quadrant and size of the tumors are important prognostic factors to predict axillary node metastasis without the need of sentinel node biopsy in early breast cancers.

TP8.1.1 Does ultrasound quantification of suspicious axillary nodes correlate with pathological results?

Aims Fast-track axillary node clearance (ANC) leads to overtreatment of axilla. Improved quantification by axillary US (AUS) is suggested to avoid unnecessary ANC and proceed with ANC or SLNB based on the number of abnormal axillary nodes. This retrospective study was aimed to evaluate whether ANC can be omitted based on AUS quantification in patients with low axillary burden. Methods Retrospective data of breast cancer patients who underwent ANC following a positive pre-operative axillary nodal biopsy between 1 January 2017 and 31 December 2018 were included in this study. The patients who received neoadjuvant chemotherapy, those having ANC following positive SLNB and those with axillary recurrence were excluded. The histopathology results of ANC were correlated with axillary ultrasound findings. Results 45 patients underwent fast-track ANC following positive axillary core biopsy. On pre-operative AUS, 18 of these patients were reported to have a single abnormal node, while 8 had two abnormal nodes and 19 patients had multiple abnormal nodes. The comparison of the number of metastatic nodes following ANC, and the reported abnormal nodes on pre-operative AUS, showed that 57.3% of patients with 1 – 2 abnormal nodes on AUS had 3 or more metastatic nodes and 26.3% of patients with multiple abnormal nodes on AUS had 1 – 2 metastatic nodes following ANC. Conclusions The quantification of the axillary burden with pre-operative AUS does not correlate with the number of metastatic axillary nodes. The reported relevant axillary burden on AUS is not sufficiently specific to form the basis of omission of ANC.

EP.TH.515A Case of mucinous adenocarcinoma of the breast in a young male patient presenting with a subcutaneous axillary lump

Aims Mucinous adenocarcinoma of the breast is rarely encountered clinically, and makes up only 0.01% of Breast cancer (BC) cases and &lt; 1% of male breast cancer (MBC). We describe an extremely rare case of mucinous carcinoma in accessory axillary breast tissue in a male. Case details A 48-year old male presented with a subcutaneous lump in his left axilla. Ultrasound described a 30mm hypoechoic mass and core biopsy confirmed mucinous adenocarcinoma, strongly positive for oestrogen and progesterone receptors, HER2 negative. A solitary enlarged axillary node in was sampled (C2) and mammogram reported a 32mm spiculate mass (M4) on the left. PET scan showed uptake only in the known axillary mass. Management Wide Local Excision and Sentinel Lymph Node Biopsy (SLNB) was completed. Histology showed a 27 mm grade 2 mucinous carcinoma, and the patient completed adjuvant radiotherapy and was commenced on tamoxifen. Conclusions MBC is rare, and accounts for only 1% of all BC. Men tend to be diagnosed at an older age (mean is 67 years) and usually have genetic/hormonal risk factors. Histologically, invasive ductal carcinoma makes up 95% of MBC. In every regard therefore, our case breaks the mold since, he was young, had no genetic/family history and no background of gynaecomastia (present in 6-38%). Literature review suggests that this is only the second case of its kind and from it we can learn to be vigilant for MBC in accessory axillary breast tissue as well as the more typical presentations.

EP.TH.166Evaluation of the impact of the COVID-19 pandemic on the practice of axillary node dissection

Aims The Association of Breast Surgery's "COVID-altered" guidance for management of breast cancer during the COVID-19 pandemic, includes that neoadjuvant chemotherapy was only to be used only in inoperable disease and not to downstage the axilla. Delayed presentation with increased nodal involvement was also a concern. We aim to establish if axillary node dissection (AND) increased in the context of pandemic. Methods Patients undergoing surgery for breast cancer were identified from theatre coding in a UK breast unit. Pre-COVID (March 2018 - February 2020) and COVID pandemic (March - September 2020) cohorts were compared. Indication, tumour receptor status, neoadjuvant chemotherapy (NAC) and deviation from routine practice were ascertained for those undergoing AND. Trust Caldicott and audit department approval was obtained for this retrospective review of practice. Results AND was performed in 20.2% (23/114) of breast cancer operations during the pandemic compared with 18.97% (78/411) pre-COVID. Indication for AND during the pandemic and pre-COVID respectively - clinically node positive 82.6%/79.4%; positive sentinel node biopsy 4.3%/17.9%; recurrence or metastases from contralateral cancer 13%/2.5%. NAC preceded AND in 30% of cases in both cohorts. NAC for one node positive HER2+ cancer was omitted due to the pandemic and another patient had adjuvant chemotherapy omitted for a HER2+ cancer with a single positive sentinel node mandating an AND which yielded no further positive nodes. Conclusions The COVID-19 pandemic has not significantly impacted rates of AND in our practice. However, we identified 2 patients who may have avoided AND with normal chemotherapy protocols.

EP.TH.879Does ‘fast -track’ axillary node clearance following positive core biopsy lead to overtreatment of axilla?

Aims Axillary node clearance (ANC) can cause lifelong disability and conservative axillary dissection is increasingly preferred. However, direct (fast-track) ANC after preoperative axillary biopsy is still performed, which may be overtreating the patients with low axillary burden. This study aims to identify if direct (fast- track) ANC leads to overtreatment of axilla. Methods Retrospective data for all breast cancer patients who underwent surgery between 1 January 2017 and 31 December 2018 were included in this study. The histopathology results of ANC were correlated with axillary ultrasound findings, axillary biopsy or SLNB results and effect of neoadjuvant treatment. These were analysed against the available guidelines to evaluate the current practice. Results 82 patients out of 520 had ANC (15.7%). Four groups were identified. 35.5% of patients diagnosed with nodal infiltration on preoperative biopsy (Group A) had only 1- 2 positive nodes following ANC. Complete pathological response was observed in 37.5% patients with nodal infiltration who had ANC following neoadjuvant chemotherapy (NACT) (Group B). No further nodes were subsequently found in 63.6% of patients who underwent ANC following positive SLNB (Group C). Group D included 2 patients with axillary recurrence. Conclusions 15.7% of breast cancer patients required ANC. The practice of direct (fast-track) ANC after axillary biopsy leads to overtreatment of the axilla, which needs re-evaluation. Targeted axillary dissection could avoid unnecessary axillary dissection in patients with abnormal nodes. This is now recommended in patients who have received NACT but has not been evaluated yet in patients with up front surgery.

Four PAX5 Negative Nodular Sclerosing Hodgkins Lymphoma Case Series

Introduction/Objective Hodgkins lymphoma is a B cell lymphoproliferative disease, with most cases showing PAX5 positivity. Very few PAX5 negative hodgkins lymphoma cases have been described. We describe four PAX5 negative nodular sclerosing hodgkins lymphoma cases. All received standard chemotherapy, three received additional chemotherapeutic agents. Exploring these rare cases can be invaluable in characterizing and later treating his atypical presentation. Methods/Case Report Four cases of Hodgkins Lymphoma were diagnosed between 2017 and 2020. Two males and two females between 31 and 80 year old. Case 1 was a 31 year old male with a left neck lymphadenopathy that revealed nodular sclerosing Hodgkins lymphoma without bone marrow involvement. IHC staining revealed CD15, CD30, fascin and MUM-1 positivity, and PAX5 negativity. He received Doxorubicin, Vinblastine, Dacarbazine (AVD) and Brentuximab with radiation, and later brentuximab with bendamutine. Follow up PET-CT and left axillary node excisional biopsy found nodular sclerosing classic hodgkins. He received Ifosfamide, Carboplatin, and Etoposide. Case 2 was a 37 year old male with bilateral mediastinal lymphadenopathy that demonstrated nodular sclerosing Hodgkins lymphoma on biopsy. The cells were CD15, CD30 positive, and PAX5 negative. He received AVD with bleomycin (ABVD), and field radiation with excellent response and is currently under surveillance. Case 3 was a 31 year old female with a left chest mass that demonstrated nodular sclerosing Hodgkins lymphoma. The cells were positive for MUM1, CD30 and fascin and negatively for CD15 and PAX5. She received ABVD. Case 4 was an 80 year old female with prior stage IV gastric diffuse large B cell lymphoma treated with Rituximab, Cyclophophamide, Vincristine, and Prednisone and achieved remission. She later developed neck masses that were biopsied revealing classic Hodgkins lymphoma. The cells stained for CD30, for CD15, and were negative for PAX5. She was started on AVD and is on palliative care. Results (if a Case Study enter NA) NA Conclusion Most hodgkins lymphomas are PAX5 positive. We found four cases of PAX5 negative Hodgkins lymphoma. Incidentally, all were of the nodular sclerosing subtype. All cases were treated with recommended chemotherapy and/or radiation. All four cases had good response with reduction in disease burden. This finding suggests that PAX5 negativity still allows the nodular sclerosing hodgkins lymphoma to be responsive to standard treatment modalties.

EP.TH.930Contemporary trends in the management of micrometastatic axillary disease in the setting of mastectomy – a 5 year single institution experience

Background Since the ACOSOG Z0011 trial, rates of axillary node clearance (ANC) for micrometastatic axillary disease have declined among women undergoing breast conservation surgery (BCS). However, for women undergoing mastectomy, it remains unclear whether omission of ANC is a safe and feasible option. Aims Identify current practice relating to management of the axilla in women with early stage, clinically node negative breast cancer, found to have micrometastatic disease on SNB, who undergo mastectomy Methods From 2013 to 2017 patients with clinical T1-T2Nmi breast cancer undergoing upfront surgery were identified from a prospective institutional database. Receipt of adjuvant radiotherapy or subsequent ANC were assessed. Patients who received neoadjuvant chemotherapy or BCS were excluded. Results 47 patients undergoing mastectomy for ESBC had micrometastasis identified on SNB. The majority of tumours had invasive ductal histology. 16/27 women underwent completion ANC (34%). Six patients had further nodal disease identified in the ANC specimen. 2 had &gt;5 nodes positive. During the study period 31 patients (65%) received adjuvant radiotherapy. Of the patients who did not undergo ANC, 21 (67.7%) received adjuvant radiotherapy. Conclusion At this institution the majority of patients requiring mastectomy with micrometastatic disease on SNB do not undergo subsequent ANC (&gt;60%). Although this is a small patient cohort, these data indicate the rate of residual axillary disease is low, and are in keeping with trends in the literature, and may help inform management decisions in this patient group.