Timing of Chemotherapy and Patient-Reported Outcomes After Breast-Conserving Surgery and Mastectomy with Immediate Reconstruction.

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR). METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression. RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis. CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

Contrast-enhanced mammography in the assessment of residual disease after neoadjuvant treatment.

PURPOSE: To investigate the utility of contrast-enhanced mammography (CEM) as an alternative to breast MRI for the evaluation of residual disease after neoadjuvant treatment (NAT). METHODS: This prospective study enrolled consecutive women undergoing NAT for breast cancer from July 2017-July 2019. Breast MRI and CEM exams performed after completion of NAT were read independently by two breast radiologists. Residual disease and lesion size on MRI and CEM recombined (RI) and low-energy images (LEI) were compared. Histopathology was considered the reference standard. Statistical analysis was performed using McNemar's and Leisenring's tests. Multiple comparison adjustment was made using Bonferroni procedure. Lesion sizes were correlated using Kendall's tau coefficient. RESULTS: There were 110 participants with 115 breast cancers. Residual disease (invasive cancer or ductal carcinoma in situ) was detected in 83/115 (72%) lesions on pathology, 71/115 (62%) on MRI, 55/115 (48%) on CEM RI, and 75/115 (65%) on CEM LEI. When using multiple comparison adjustment, no significant differences were detected between MRI combined with CEM LEI and CEM RI combined with CEM LEI, in terms of accuracy (MRI: 77%, CEM: 72%; p ≥ 0.99), sensitivity (MRI: 88%, CEM: 81%; p ≥ 0.99), specificity (MRI: 47%, CEM: 50%; p ≥ 0.99), PPV (MRI: 81%, CEM: 81%; p ≥ 0.99), or NPV (MRI: 60%, CEM: 50%; p ≥ 0.99). Size correlation between pathology and both MRI combined with CEM LEI and CEM RI combined with CEM LEI was moderate: τ = 0. 36 vs 0.33 (p ≥ 0.99). CONCLUSION: Contrast-enhanced mammography is an acceptable alternative to breast MRI for the detection of residual disease after neoadjuvant treatment.

How Much Pain Will I Have After Surgery? A Preoperative Nomogram to Predict Acute Pain Following Mastectomy.

INTRODUCTION: Acute postoperative pain affects time to opioid cessation and quality of life, and is associated with chronic pain. Effective screening tools are needed to identify patients at increased risk of experiencing more severe acute postoperative pain, and who may benefit from multimodal analgesia and early pain management referral. In this study, we develop a nomogram to preoperatively identify patients at high risk of moderate-severe pain following mastectomy. METHODS: Demographic, psychosocial, and clinical variables were retrospectively assessed in 1195 consecutive patients who underwent mastectomy from January 2019 to December 2020 and had pain scores available from a post-discharge questionnaire. We examined pain severity on postoperative days 1-5, with moderate-severe pain as the outcome of interest. Multivariable logistic regression was performed to identify variables associated with moderate-severe pain in a training cohort of 956 patients. The final model was determined using the Akaike information criterion. A nomogram was constructed using this model, which also included a priori selected clinically relevant variables. Internal validation was performed in the remaining cohort of 239 patients. RESULTS: In the training cohort, 297 patients reported no-mild pain and 659 reported moderate-severe pain. High body mass index (p = 0.042), preoperative Distress Thermometer score ≥4 (p = 0.012), and bilateral surgery (p = 0.003) predicted moderate-severe pain. The resulting nomogram accurately predicted moderate-severe pain in the validation cohort (AUC =  0.735). CONCLUSIONS: This nomogram incorporates eight preoperative variables to provide a risk estimate of acute moderate-severe pain following mastectomy. Preoperative risk stratification can identify patients who may benefit from individually tailored perioperative pain management strategies and early postoperative interventions to treat pain and assist with opioid tapering.

Association Between Local Anesthetic Dosing, Postoperative Opioid Requirement, and Pain Scores After Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

BACKGROUND: Multimodal analgesia (MMA) during breast surgery reduces postoperative pain and opioid requirements, but the relative contribution of local anesthetic dosing as a component of MMA is not well defined among patients undergoing lumpectomy and sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: We identified consecutive patients who underwent lumpectomy and SLNB with MMA from 1/2019 to 4/2020. Univariable and multivariable linear and logistic regression were used to examine associations between local anesthetics, opioid requirements in the post-anesthesia care unit (PACU), and pain scores in the PACU and on postoperative day (POD) 1. RESULTS: In total, 1603 patients [median tumor size, 14 mm (interquartile range 8-20 mm)] were included. The median PACU opioid requirement was 0 morphine milligram equivalents (interquartile range 0-5). PACU maximum pain was none or mild in 58% of patients and moderate to severe in 42%; among 420 survey respondents, 56% reported no or mild pain and 44% reported moderate to severe pain on POD 1. On multivariable analysis that adjusted for routine components of MMA, increasing doses of 0.5% bupivacaine were associated with reduced PACU opioid requirements (ß -0.04, 95% confidence interval -0.07 to -0.01, p = 0.011) and lower odds of moderate to severe pain (odds ratio 0.98, 95% confidence interval 0.97-0.99, p < 0.001). Local anesthetics were not associated with pain scores on POD 1. CONCLUSIONS: Higher amounts of local anesthetics reduce acute postoperative pain and opioid requirement after lumpectomy and SLNB. Maximizing dosing within weight-based limits is a low-risk, cost-effective pain control strategy that can be used in diverse practice settings.

Nodal Recurrence in Patients With Node-Positive Breast Cancer Treated With Sentinel Node Biopsy Alone After Neoadjuvant Chemotherapy-A Rare Event.

IMPORTANCE: Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. OBJECTIVE: To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. DESIGN, SETTING, AND PARTICIPANTS: From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center. INTERVENTION: Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. MAIN OUTCOME AND MEASURES: The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. RESULTS: Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences. CONCLUSIONS AND RELEVANCE: This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

Postdischarge Nonsteroidal Anti-Inflammatory Drugs Are not Associated with Risk of Hematoma after Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly used in ambulatory breast surgery. The risk of hematoma associated with intraoperative ketorolac is low, but whether concomitant routine discharge with NSAIDs increases the risk of hematoma is unclear. METHODS: We retrospectively identified patients who underwent lumpectomy and sentinel lymph node biopsy (SLNB), and compared the 30-day risk of hematoma between patients discharged with opioids (opioid period: January 2018-August 2018) and patients discharged with NSAIDs with or without opioids (NSAID period: January 2019-April 2020). The association between study period and hematoma risk was assessed using multivariable models. Covariates included intraoperative ketorolac, home aspirin, and race/ethnicity. During the NSAID period, a survey was used to assess analgesic consumption on postoperative days 1-5. RESULTS: In total, 2724 patients were identified: 858 (31%) in the opioid period and 1866 (69%) in the NSAID period. In the NSAID period, 867 (46%) received NSAIDs and opioids, and 999 (54%) received NSAIDs only. Receipt of intraoperative ketorolac was higher in the NSAID period (78 vs. 64%, P < 0.001). The risks of any hematoma (4.1 vs. 3.6%, P = 0.6) and reoperation for bleeding (0.5 vs. 0.6%, P = 0.8) were similar between groups. Study period was not associated with hematoma risk (odds ratio 0.87, 95% confidence interval 0.56-1.35, P = 0.5). Among survey respondents (41%), nonopioid analgesic consumption did not increase after opioids were removed from the discharge regimen (median, 6 pills/group, P = 0.06). CONCLUSIONS: NSAIDs are associated with a low risk of hematoma after lumpectomy and SLNB, and should be prescribed instead of opioids, unless contraindicated.

Patterns of invasive recurrence among patients originally treated for ductal carcinoma in situ by breast-conserving surgery versus mastectomy.

PURPOSE: Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy. METHODS: From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy. RESULTS: 452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p < 0.001) compared with the BCS group. A higher proportion of invasive recurrences were local after BCS (93%; 343/367), whereas 88% (75/85) of recurrences after mastectomy were regional or distant (p < 0.001). The median time to first invasive recurrence was not different between surgical groups (BCS: 6.4 years vs. mastectomy: 5.5 years; p = 0.12). CONCLUSIONS: Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.

Effects of Adiposity and Exercise on Breast Tissue and Systemic Metabo-Inflammatory Factors in Women at High Risk or Diagnosed with Breast Cancer.

Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality, including in normal weight women. To investigate underlying mechanisms, we examined whether adiposity and exercise impact the breast microenvironment (e.g., inflammation and aromatase expression) and circulating metabo-inflammatory factors. In a cross-sectional cohort study, breast white adipose tissue (WAT) and blood were collected from 100 women undergoing mastectomy for breast cancer risk reduction or treatment. Self-reported exercise behavior, body composition measured by dual-energy x-ray absorptiometry (DXA), and waist:hip ratio were obtained prior to surgery. Breast WAT inflammation (B-WATi) was assessed by IHC and aromatase expression was assessed by quantitative PCR. Metabolic and inflammatory blood biomarkers that are predictive of breast cancer risk and progression were measured. B-WATi was present in 56 of 100 patients and was associated with older age, elevated BMI, postmenopausal status, decreased exercise, hypertension and dyslipidemia (Ps < 0.001). Total body fat and trunk fat correlated with B-WATi and breast aromatase levels (Ps < 0.001). Circulating C-reactive protein, IL6, insulin, and leptin positively correlated with body fat and breast aromatase levels, while negative correlations were observed for adiponectin and sex hormone binding globulin (P < 0.001). Inverse relationships were observed with exercise (Ps < 0.05). In a subgroup of 39 women with normal BMI, body fat levels positively correlated with B-WATi and aromatase expression (Ps < 0.05). In conclusion, elevated body fat levels and decreased exercise are associated with protumorigenic micro- and host environments in normal, overweight, and obese individuals. These findings support the development of BMI-agnostic lifestyle interventions that target adiposity. PREVENTION RELEVANCE: We report that individuals with high body fat and low exercise levels have breast inflammation, higher breast aromatase expression, and levels of circulating metabo-inflammatory factors that have been associated with increased breast cancer risk. These findings support interventions to lower adiposity, even among normal weight individuals, to prevent tumor growth.

Routine Opioid Prescriptions Are Not Necessary After Breast Excisional Biopsy or Lumpectomy Procedures.

BACKGROUND: Opioid analgesics are overprescribed after surgery. In August 2018, the authors replaced routine discharge opioid prescription with a nonsteroidal anti-inflammatory drug (NSAID) for patients who had a lumpectomy or excisional biopsy (lump/ex). This study compared patient-reported post-discharge pain scores for patients treated before and after the change in routine discharge medication. METHODS: Patients were categorized based on treatment before and after a change in discharge medication as follows: study period 1 (routine opioids), study period 2 (routine NSAID). Pain severity was assessed with an electronic survey on postoperative days (PODs) 1 to 5. Multivariable generalized estimating equations tested the association between pain severity and discharge in the first versus the second study period. RESULTS: Lump/ex was performed for 1606 patients between December 2017 and June 2019. Of these patients, 789 (49%) reported pain scores and were analyzed (328 in study period 1, 461 in study period 2). Opioid prescription at discharge decreased from 96% in period 1 to 14% (95% confidence interval [CI], 11-18%) in period 2. Only 1% of the patients discharged with NSAID were later prescribed an opioid. The maximum reported pain score on any POD for all the patients was severe for 30 patients (3.8%), moderate for 217 patients (28%), mild for 430 patients (54%), and none for 112 patients (14%). The estimated risk for moderate or greater pain on POD 1 was 36% for period 1 and 34% for period 2. The proportion of patients reporting moderate or greater pain was nonsignificantly lower for the patients treated in period 2 (odds ratio [OR], 0.91; 95% CI 0.67-1.22; P = 0.5). CONCLUSIONS: For patients undergoing lump/ex, a clinically meaningful difference in reported post-discharge pain scores can be excluded with a change to routine NSAID at discharge. Patients undergoing lump/ex should not be routinely discharged with opioids.

Changing the Default: A Prospective Study of Reducing Discharge Opioid Prescription after Lumpectomy and Sentinel Node Biopsy.

BACKGROUND: Whether routinely prescribed opioids are necessary for pain control after discharge among lumpectomy/sentinel node biopsy (Lump/SLNB) patients is unclear. We hypothesize that Lump/SLNB patients could be discharged without opioids, with a failure rate < 10%. This study prospectively examines outcomes after changing standard discharge prescription from an opioid/non-steroidal anti-inflammatory drug (NSAID) to NSAID/acetaminophen. PATIENTS AND METHODS: Standard discharge pain medication orders included opioids in the first 3-month study period and were changed to NSAID/acetaminophen in the second 3-month period. Patient-reported medication consumption and pain scores were collected by post-discharge survey. Frequency of discharge with opioid, NSAID/acetaminophen failure rate, opioid use, and pain scores were examined. RESULTS: From May to October 2019, 663 patients had Lump/SLNB: 371 in the opioid study period and 292 in the NSAID period. In the opioid period, 92% (342/371) of patients were prescribed an opioid at discharge; of 142 patients who documented opioid use on the survey, 86 (61%) used zero tablets. Among 56 (39%) patients who used opioids, the median number taken by POD 5 was 4. After the change to NSAID/acetaminophen, rates of opioid prescription decreased to 14% (41/292). The NSAID/acetaminophen failure rate was 2% (5/251). Among survey respondents, there was no significant difference in the maximum reported pain scores (POD 1-5) between the opioid period and the NSAID period (p = 0.7). CONCLUSIONS: In Lump/SLNB patients, a change to default discharge with NSAID/acetaminophen resulted in a 78% absolute reduction in opioid prescription, with a failure rate of 2% and no difference in patient-reported pain scores. Most Lump/SLNB patients can be discharged with NSAID/acetaminophen.

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.

PURPOSE: Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. METHODS AND MATERIALS: Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. RESULTS: After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. CONCLUSIONS: This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.

B-Sure: a randomized pilot trial of an interactive web-based decision support aid versus usual care in average-risk breast cancer patients considering contralateral prophylactic mastectomy.

The use of contralateral prophylactic mastectomy (CPM) is increasing among breast cancer patients who are at average or "sporadic" risk for contralateral breast cancer. Because CPM provides no survival benefit for these patients, it is not medically recommended for them. Decision support aids may facilitate more informed, higher quality CPM decision. The purpose of this study was to evaluate the feasibility and acceptability of B-Sure, an online decision support aid to facilitate informed decisions regarding CPM, and to compare the impact of B-Sure in increasing CPM knowledge, reducing decisional conflict, and increasing preparedness to make the CPM decision among breast cancer patients at sporadic risk who are considering CPM. Ninety-three patients with unilateral, nonhereditary breast cancer considering CPM completed a baseline survey, were randomized to receive B-Sure or Usual care, and completed a 4-week follow-up survey assessing decisional conflict, preparedness to make the CPM decision, and CPM knowledge as well as self-efficacy, perceived risk, worry, CPM motivations, and the surgical decision. Study participation was high. B-Sure was viewed by almost 80% of the participants and was evaluated positively. At follow-up, patients assigned to B-Sure reported significantly higher clarity regarding the personal values relevant to the CPM decision and higher knowledge about CPM. B-Sure had smaller effects on other aspects of decisional conflict. B-Sure improved CPM knowledge and reduced decisional conflict. Patients considering CPM may benefit from an online decision support aid, but may be sensitive to approaches that they perceive as biased against CPM.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients.

BACKGROUND: In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. METHODS: Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). RESULTS: Median patient age was 58 years, and median tumor size was 1.7 cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41 months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. CONCLUSIONS: In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Genomic comparison of paired primary breast carcinomas and lymph node macrometastases using the Oncotype DX Breast Recurrence Score® test.

PURPOSE: Adjuvant therapy decisions may in part be based on results of Oncotype DX Breast Recurrence Score® (RS) testing of primary tumors. When necessary, lymph node metastases may be considered as a surrogate. Here we evaluate the concordance in gene expression between primary breast cancers and synchronous lymph node metastases, based on results from quantitative RT-PCR-based RS testing between matched primary tumors and synchronous nodal metastases. METHODS: This retrospective, exploratory study included patients (≥ 18 years old) treated at our center (2005-2009) who had ER+ , HER2-negative invasive breast cancer and synchronous nodal metastases with available tumor blocks from both sites. Paired tissue blocks underwent RS testing, and RS and single-gene results for ER, PR, and HER2 were explored between paired samples. RESULTS: A wide distribution of RS results in tumors and in synchronous nodal metastases were modestly correlated between 84 paired samples analyzed (Pearson correlation 0.69 [95% CI 0.55-0.78]). Overall concordance in RS group classification between samples was 63%. ER, PR, and HER2 by RT-PCR between the primary tumor and lymph node were also modestly correlated (Pearson correlation [95% CI] 0.64 [0.50-0.75], 0.64 [0.49-0.75], and 0.51 [0.33-0.65], respectively). Categorical concordance (positive or negative) was 100% for ER, 77% for PR, and 100% for HER2. CONCLUSIONS: There is modest correlation in continuous gene expression, as measured by the RS and single-gene results for ER, PR, and HER2 between paired primary tumors and synchronous nodal metastases. RS testing for ER+ breast cancer should continue to be based on analysis of primary tumors.

Decisional conflict among breast cancer patients considering contralateral prophylactic mastectomy.

OBJECTIVES: The study's goals were to characterize decisional conflict and preparedness for making the decision about having CPM among breast cancer patients considering CPM who do not carry cancer-predisposing mutation and to evaluate correlates of decisional conflict and preparedness. METHODS: 93 women considering CPM completed a survey of decisional conflict and preparedness for the CPM decision, knowledge, perceived risk, self-efficacy, reasons for CPM, input from others and discussion with the doctor about CPM, and cancer worry. RESULTS: Between 8% and 27% of women endorsed elevated decisional conflict. Most women were satisfied with preparatory information that they were provided. Knowledge was low. Top reasons for choosing CPM were the desire for peace of mind, lowering the chance of another breast cancer, and improving survival. CONCLUSIONS: Decisional conflict is elevated in a subset of patients considering CPM. A more well-informed decision may be fostered by a comprehensive discussion about CPM with the patient's clinician, fostering self-efficacy in managing cancer worry, and helping patients understand their motivations for CPM. PRACTICE IMPLICATIONS: Clinicians working with breast cancer patients considering CPM should discuss the CPM decision, foster self-efficacy in managing cancer worry, and help patients understand their motivations for the surgery.

Breast-conservation Therapy After Neoadjuvant Chemotherapy Does Not Compromise 10-Year Breast Cancer-specific Mortality.

OBJECTIVES: Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery by downstaging disease in patients with breast cancer. The aim of this study was to determine whether patients who received neoadjuvant chemotherapy have equal survival after breast-conservation therapy compared with mastectomy. MATERIAL AND METHODS: Using the New Jersey State Cancer Registry (NJSCR) patients with a primary breast cancer diagnosed between 1998 and 2003 who underwent neoadjuvant chemotherapy were selected (n=1,468). Of those, only patients who received lumpectomy plus radiation (n=276) or mastectomy without radiation (n=442) were included in the analysis. The main outcome measured included 10-year breast cancer-specific mortality, with 90% of patients with known vital status through the end of 2011. RESULTS: Baseline characteristics did not differ significantly between the breast-conservation and mastectomy without radiation groups except with respect to summary stage and lymph node involvement. After propensity score matching these differences were no longer statistically significant; however, both estrogen and progesterone status achieved statistical significance. The Kaplan-Meier survival curve showed that the breast-conservation group had significantly higher breast cancer-specific survival than the mastectomy group (P=0.0046). After adjusting for the propensity score in the regression model, the breast-conservation group continued to show significantly better survival than the mastectomy group (hazard ratios, 0.46; 95% confidence interval, 0.27-0.78). CONCLUSIONS: This study is consistent with previous research showing that breast-conserving surgery after neoadjuvant chemotherapy does not reduce breast cancer-specific survival. In fact, patients undergoing breast-conservation after neoadjuvant therapy appeared to have better survival than patients undergoing mastectomy without radiation.

Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients.

OBJECTIVE: To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. BACKGROUND: Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1 to 2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. METHODS: Patients eligible for Z0011 had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t tests. Cumulative incidence of recurrences was estimated with competing risk analysis. RESULTS: From August 2010 to December 2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. Among them, 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. Five-year event-free survival after SLN alone was 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast + nodal and nodal + distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast + nodes) and follow-up ≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. CONCLUSIONS: We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

Hypofractionated Postmastectomy Radiation Therapy Is Safe and Effective: First Results From a Prospective Phase II Trial.

Purpose Conventionally fractionated postmastectomy radiation therapy (PMRT) takes approximately 5 to 6 weeks. Data supporting hypofractionated PMRT is limited. We prospectively evaluated a short course of hypofractionated PMRT, in which therapy was completed in 15 treatment days. Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes, followed by an optional mastectomy scar boost of four fractions of 3.33 Gy. Our primary end point was freedom from any grade 3 or higher toxicities. We incorporated early stopping criteria on the basis of predefined toxicity thresholds. Results We enrolled 69 women with stage II to IIIa breast cancer, of whom 67 were eligible for analysis. After a median follow-up of 32 months, there were no grade 3 toxicities. There were 29 reported grade 2 toxicities, with grade 2 skin toxicities being the most frequent (16 of 67; 24%). There were two patients with isolated ipsilateral chest wall tumor recurrences (2 of 67; crude rate, 3%). Three-year estimated local recurrence-free survival was 89.2% (95% CI, 0.748 to 0.956). The 3-year estimated distant recurrence-free survival was 90.3% (95% CI, 0.797 to 0.956). Forty-one patients had chest wall reconstructions; three had expanders removed for infection before radiation therapy. The total rate of implant loss or failure was 24% (9 of 38), and the unplanned surgical correction rate was 8% (3 of 38), for a total complication rate of 32%. Conclusion To our knowledge, our phase II prospective study offers one of the shortest courses of PMRT reported, delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost. We demonstrated low toxicity and high local control with this schedule. On the basis of our data, we have designed a cooperative group phase III prospective, randomized trial of conventional versus hypofractionated PMRT that will activate soon.