Physical health-related quality of life trajectories over two years following breast cancer diagnosis in older women: a secondary analysis.

PURPOSE: To identify distinct trajectories of physical health-related quality of life (HRQoL) in older women over the first two years following breast cancer diagnosis, and to examine characteristics associated with trajectory group membership. METHODS: A secondary analysis of a longitudinal study of women diagnosed with stage I-III breast cancer who completed surveys within eight months of diagnosis and six, twelve, and eighteen months later that focuses on a subset of women aged ≥ 65 years (N = 145).Physical HRQoL was assessed using the Physical Component Score (PCS) of the SF-36 Health Survey. Finite mixture modeling identified distinct PCS trajectories. Multivariable logistic regression identified variables predictive of low PCS group membership. RESULTS: Two distinct patterns of PCS trajectories were identified. The majority (58%) of women had PCS above the age-based SF-36 population norms and improved slightly over time. However, 42% of women had low PCS that remained low over time. In multivariable analyses, older age, difficulty paying for basics, greater number of medical comorbidities, and higher body mass index were associated with low PCS group membership. Cancer treatment and psychosocial variables were not significantly associated. CONCLUSION: A large subgroup of older women reported very low PCS that did not improve over time. Older age, obesity, multiple comorbidities, and lower socioeconomic status may be risk factors for poorer PCS in women with breast cancer. Incorporating routine comprehensive geriatric assessments that screen for these factors may help providers identify older women at risk for poorer physical HRQoL post breast cancer treatment.

Factors associated with insomnia symptoms over three years among premenopausal women with breast cancer.

PURPOSE: We examined longitudinal trends and factors associated with insomnia over 3 years in a cohort of young breast cancer patients. METHODS: Women with stage I-III breast cancer at ≤ 45 years were recruited at five institutions from New York, Texas, and North Carolina, within 8 months of diagnosis (n = 836). Participants completed questionnaires every 6 months for 3 years. Linear mixed-effects models were used to examine insomnia over time, using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). We evaluated the relations of insomnia with demographic (age, race, education, income, employment, marital status), clinical (cancer stage, histologic grade, chemotherapy, radiation, hormone therapy, surgery, tumor size, body mass index, hot flashes), and social/behavioral variables (smoking status, social support, physical activity, depressive symptoms). RESULTS: At baseline, 57% of participants met or exceeded the cut-off for clinical insomnia (WHIIRS score ≥ 9). Insomnia symptoms were most prevalent at baseline (p < 0.0001), but decreased significantly throughout follow-up (p < 0.001). However, 42% of participants still experienced insomnia symptoms 3 years after diagnosis. In multivariable models, older age (p = 0.02), hot flashes (p < 0.0001), and depressive symptoms (p < 0.0001) remained significantly associated with insomnia over time. CONCLUSIONS: Insomnia symptoms were most frequent closer to breast cancer diagnosis and treatment, but persisted for some women who were older and those reporting higher hot flashes and depressive symptoms. Survivorship care should include assessing insomnia symptoms, particularly during and immediately after primary treatment. Implementing early interventions for sleep problems may benefit young breast cancer survivors and improve their quality of life.

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.

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.

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.

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.

Intraoperative Ketorolac is Associated with Risk of Reoperation After Mastectomy: A Single-Center Examination.

BACKGROUND: Although ketorolac is an effective adjunct for managing pain in the perioperative period, it is associated with a risk of postoperative bleeding. This study retrospectively investigated the association between ketorolac use and both reoperation and postoperative opioid use among mastectomy patients. METHODS: The study identified all women undergoing mastectomy (unilaterally or bilaterally) at our ambulatory surgery cancer center from January 2016 to June 2019. The primary outcome was reoperation for bleeding on postoperative day 0 or 1, and the secondary outcome was postoperative opioid use. The association between ketorolac and outcomes was assessed using multivariable regression models. The covariates were age, body mass index, breast reconstruction, bilateral surgery, peripheral nerve block, and preoperative antiplatelet and/or anticoagulation medication. RESULTS: A cohort of 3469 women were identified. Ketorolac was given to 1549 (45%) of the women, with 922 women (60%) receiving 30 mg and 627 women (40%) receiving 15 mg. The overall reoperation rate for bleeding was 3.1% (1.8% without ketorolac vs 4.8% with ketorolac). In the multivariable analysis, ketorolac was associated with a higher risk of reoperation [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.60-3.70; P < 0.0001]. Ketorolac also was associated with a lower proportion of patients receiving any postoperative narcotic within 24 h (15 mg: OR 0.73; 95% CI 0.57-0.94; P = 0.014 vs 30 mg: OR 0.52; 95% CI 0.42-0.66; P < 0.0001). CONCLUSIONS: Ketorolac use decreased postoperative opioid use, but this benefit was outweighed by the increased risk of bleeding requiring reoperation. This finding led to a change in practice at the authors' center, with ketorolac no longer administered in the perioperative care of the mastectomy patient.

Atypical ductal hyperplasia bordering on DCIS on core biopsy is associated with higher risk of upgrade than conventional atypical ductal hyperplasia.

PURPOSE: Upgrade rates of conventional ADH are reported at 10-30%; however, rates for ADH bordering on DCIS (ADH-BD) are largely unknown. We examined the upgrade rate of ADH-BD and core needle biopsy (CNB) features associated with upgrade. Surgical management in patients with concurrent ipsilateral breast cancer (BC) was also examined. METHODS: From 2000 to 2018, women with CNB diagnosis of ADH-BD were prospectively identified. Women with pure ADH-BD and concurrent ipsilateral ADH-BD/BC were analyzed separately, and upgrade rates were calculated. CNB features associated with upgrade and type of surgery were examined in women with pure ADH-BD; CNB features and concurrent pathology associated with upgrade were examined in women with ipsilateral BC. RESULTS: 108/236 (46%) patients with pure ADH-BD on CNB had DCIS (40%) or invasive carcinoma (6%) on surgical excision. DCIS or invasive carcinoma was more frequently found on excision of a mass that yielded ADH-BD on biopsy than excision of calcifications (65% vs 38%; p < 0.001). The breast conservation success rate was high (80%) in patients who upgraded, despite a high re-excision rate of 46%. The upgrade rate of ADH-BD in women with concurrent ipsilateral BC was 41%. Most women (94%) with ADH-BD in the same quadrant as the BC were candidates for breast conserving surgery, with a success rate of 89%. CONCLUSION: The upgrade rate for pure ADH-BD is significantly higher than that reported for women with conventional ADH, especially in women with a mass on imaging. The upgrade rate of concurrent ipsilateral ADH-BD and BC is similarly high. Excision with a margin of normal tissue and specimen inking should be routine to minimize the need for re-excision.

Cosmetic Outcomes Following Breast-Conservation Surgery and Radiation for Multiple Ipsilateral Breast Cancer: Data from the Alliance Z11102 Study.

BACKGROUND: Diagnoses of multiple ipsilateral breast cancer (MIBC) are increasing. Historically, the primary treatment for MIBC has been mastectomy due to concerns about in-breast recurrence risk and poor cosmetic outcome. The Alliance Z11102 study prospectively assessed cosmetic outcomes in women with MIBC treated with breast-conserving therapy (BCT). PATIENTS AND METHODS: Z11102 was a multicenter trial enrolling women with two or three separate sites of biopsy-proven malignancy separated by ≥ 2 cm within the same breast. Cosmetic outcome was a planned secondary endpoint. Data were collected with a four-point cosmesis survey (1 = excellent, 4 = poor) and the BREAST-Q (scored 0-100). All patients undergoing successful breast-conserving therapy were treated with whole-breast radiation. Associations were assessed with Chi square or Fisher's exact tests as appropriate. RESULTS: Cosmetic outcome data for 216 eligible women who completed therapy are included in this analysis. Of the 136 patients who completed the survey 2 years postoperatively, 70.6% (N = 96) felt the result was good or excellent, while 3.7% (N = 5) felt the result was poor. We found no significant differences in patient-reported cosmetic outcomes when stratifying by patient age, number of lesions (two or three), number of incisions, number of lumpectomies, or size of largest area of disease. Mean satisfaction score on the BREAST-Q was 77.2 at 6 months following whole-breast radiation and 73.7 at 3 years following surgery. CONCLUSIONS: BCT performed for MIBC results in good or excellent cosmesis for the majority of women. From a cosmetic perspective, BCT is a valid surgical approach to women with MIBC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01556243.

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.

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.

Prevalence and correlates of job and insurance problems among young breast cancer survivors within 18 months of diagnosis.

BACKGROUND: The prevalence and correlates of job and insurance problems were examined among a cohort of young U.S. breast cancer survivors during the first 18-months following diagnosis. METHODS: Participants were 708 women diagnosed at ≤45 years with stage I-III breast cancer. 90% were non-Hispanic white, 76% were married/partnered and 67% had ≥4-year college degree. Univariable and multivariable logistic regression examined the associations between demographic, lifestyle and clinical factors with job and insurance problems. RESULTS: 18-months after diagnosis, 56% of participants worked full-time, 16% part-time, 18% were homemakers and/or students, 4.5% were unemployed, and 2.4% were disabled. The majority (86%) had private insurance. Job-related problems were reported by 40% of women, and included believing they could not change jobs for fear of losing health insurance (35.0%), being fired (2.3%), and being demoted, denied promotion or denied wage increases (7.8%). Greater job-related problems were associated with being overweight vs. under/normal weight (p = 0.006), income <$50,000/per year (p = 0.01), and working full-time vs. part-time (p = 0.003). Insurance problems were reported by 27% of women, and included being denied health insurance (2.6%), health insurance increases (4.3%), being denied health benefit payments (14.8%) or denied life insurance (11.4%). Insurance problems were associated with being under/normal weight vs. obese (p = 0.01), not being on hormone therapy (p < 0.001), and a tumor size > 5 cm vs. < 2 cm (p = 0.01). CONCLUSIONS: Young survivors experienced significant job- and insurance-related issues following diagnosis. To the extent possible, work and insurance concerns should be addressed prior to treatment to inform work expectations and avoid unnecessary insurance difficulties.

Controversies in the Treatment of Ductal Carcinoma in Situ.

Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with "low-risk" DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.

Impact of Age on Locoregional and Distant Recurrence After Mastectomy for Ductal Carcinoma In Situ With or Without Microinvasion.

BACKGROUND: Locoregional recurrence (LRR) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is increased in young women. We examined the impact of age on LRR and distant disease after mastectomy for DCIS ± microinvasion. METHODS: We identified consecutive patients with DCIS ± microinvasion treated with mastectomy from 1995 to 2017. LRR was defined as recurrence at the ipsilateral chest wall or regional nodes. RESULTS: Overall, 3121 cases were identified, of which 421 (13.5%) had DCIS + microinvasion. Median age was 49 years and median follow-up was 6.4 years; 821 were followed for 10 or more years. Thirty-four LRRs were observed: 33 (97%) were invasive, and 23 (68%) were in the chest wall alone. Cumulative 10-year LRR incidence was 1.4%. Age < 50 years, high grade, and DCIS + microinvasion were associated with LRR (p ≤ 0.001); however, margin status was not (p = 0.14). Adjusting for grade and DCIS + microinvasion, age < 50 years (hazard ratio [HR] 14.7, 95% confidence interval [CI] 3.5-61.5; p < 0.001) was associated with LRR. Compared with women ≥ 50 years of age, women age < 40 years had the highest risk (HR 27.0, 95% CI 6.0-121), and women age 40-49 years had intermediate risk (HR 11.8, 95% CI 2.8-50.5). The cumulative 10-year LRR incidence was 4.2% for women < 40 years of age, 2.0% for women 40-49 years of age, and 0.2% for women ≥ 50 years of age. Women age < 40 years had a 10-year distant disease rate of 1.6% versus women age 40-49 years (0.7%) and women age ≥ 50 years (0.7%) (log-rank p = 0.051). Grade, DCIS + microinvasion, and margins were unassociated with distant disease. CONCLUSIONS: LRR after mastectomy for DCIS ± microinvasion is uncommon, but is more frequent among women < 50 years of age, particularly in those < 40 years of age. The 10-year LRR rate in this youngest group remains low at 4.2%. Young age is an independent risk factor for LRR after BCS or mastectomy.

Risk of Contralateral Breast Cancer in Women with Ductal Carcinoma In Situ Associated with Synchronous Ipsilateral Lobular Carcinoma In Situ.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a risk factor for breast cancer, but the effect of LCIS found in association with ductal carcinoma in situ (DCIS) is unknown. In this study, we compared contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) rates among women with DCIS with or without synchronous ipsilateral LCIS treated with breast-conserving surgery (BCS). METHODS: DCIS patients undergoing BCS from 2000 to 2011 with a contralateral breast at risk were stratified by the presence or absence of synchronous ipsilateral LCIS with the index DCIS (DCIS + LCIS vs. DCIS). Those with contralateral, bilateral, or prior ipsilateral LCIS were excluded. Associations of patient, tumor, and treatment factors with CBC and IBTR were evaluated. RESULTS: Of 1888 patients identified, 1475 (78%) had DCIS and 413 (22%) had DCIS + LCIS. At median follow-up of 7.2 (range 0-17) years, 307 patients had a subsequent first breast event; 207 IBTR and 100 CBC. The 10-year cumulative incidence of IBTR was similar in both groups: 15.0% vs. 14.2% (log-rank, p = 0.8) for DCIS + LCIS vs. DCIS, respectively. The 10-year cumulative incidence of CBC was greater in the DCIS + LCIS group: 10.9% vs. 6.1% for DCIS (log-rank, p < 0.001). After adjustment for other factors, CBC risk remained higher in DCIS + LCIS compared with DCIS (hazard ratio 2.06, 95% confidence interval 1.36-3.11, p = 0.001); there was no significant difference in IBTR risk. CONCLUSIONS: Compared with DCIS alone, DCIS + LCIS is associated with similar IBTR risk but double the risk of CBC. This finding should inform treatment decisions, in particular regarding endocrine therapy for risk reduction.

Long-Term Outcomes After Surgical Treatment of Malignant/Borderline Phyllodes Tumors of the Breast.

BACKGROUND: Malignant/borderline phyllodes tumors (PTs) are rare, and little is known about their long-term prognosis. This study sought to evaluate recurrence rates and identify factors associated with local and distant failure. METHODS: From 1957 to 2017, we identified 124 patients with 125 PTs (86 malignant and 39 borderline). Recurrence rates and survival were assessed using the Kaplan-Meier method, and correlated with clinicopathologic factors using the log-rank test. RESULTS: The median age of the patients was 44 years, and the median tumor size was 5 cm. Breast-conserving surgery was performed for 57% of the patients. At a median follow-up of 7.1 years, 14 patients experienced a locoregional recurrence (LRR), with a 10-year cumulative LRR incidence of 12%. On univariable analysis, age younger than 40 years (p = 0.02) and close/positive margins (p = 0.001) were associated with increased risk of LRR. Seven patients developed distant disease, all occurring in malignant PTs. The 10-year distant recurrence-free survival was 94%. Uniformly poor pathologic features consisting of marked stromal cellularity, stromal overgrowth, infiltrative borders, and 10 or more mitoses per 10 high-power fields (hpf) were identified in 25 PTs (20%), and all distant recurrences occurred in this group. For the patients who did not have uniformly poor features, the 10-year disease-specific survival was 100%, and the overall survival was 94% compared with 66% and 57%, respectively, among those with poor features. CONCLUSION: Malignant/borderline PTs without uniformly poor histologic features have an excellent prognosis after surgical resection, with a 10-year disease-specific survival of 100%. The presence of uniformly poor pathologic features predicts a poor prognosis. Efforts should be directed toward new treatment approaches for these tumors.

Comparison of Local Recurrence Risk Estimates After Breast-Conserving Surgery for DCIS: DCIS Nomogram Versus Refined Oncotype DX Breast DCIS Score.

BACKGROUND: A ductal carcinoma in situ (DCIS) Nomogram integrating 10 clinicopathologic/treatment factors and a Refined DCIS Score (RDS) that incorporates a genomic assay and three clinicopathologic factors (Oncotype DX DCIS Score) are available to estimate DCIS 10-year local recurrence risk (LRR). This study compared these estimates. METHODS: Patients 50 years of age or older with DCIS size 2.5 cm or smaller and a genomic assay available were identified. An RDS within 1-2% of the range of Nomogram LRR estimates obtained by assuming use and non-use of endocrine therapy (Nomogram ± ET) was defined as concordant. Assuming a 10-year risk threshold of 10% for recommending radiation, Nomogram ± ET and RDS estimates were compared, and threshold concordance was determined. RESULTS: For 54 (92%) of 59 patients, the RDS and Nomogram ± ET LRR estimates were concordant. For the remaining 5 (8%) of the 59 patients, the RDS LRR estimates were lower than the Nomogram + ET estimates, with an absolute difference of 3-8%, and thus were discordant. For these five patients, the RDS estimates of 10-year LRR were lower than 10% (range 5-8%) and the Nomogram + ET estimates were 10% or higher (range 11-14%). These five patients with both discordant and threshold-discordant estimates all had close margins (≤ 2 mm). CONCLUSIONS: Among 92% of women 50 years of age or older with DCIS size 2.5 cm or smaller, free-of-charge online Nomogram 10-year LRR estimates were concordant with those obtained using the commercially available RDS (> $4600). Among the 8% with discordant risk estimates, the RDS appeared to underestimate the LRR and may lead to inappropriate omission of radiotherapy. Unless other data show a clinically significant advantage of the RDS (Oncotype DX DCIS Score), the study data suggest that for women 50 years of age or older with DCIS size 2.5 cm or smaller, its use is not warranted.

Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ.

BACKGROUND: The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS). METHODS: Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis. RESULTS: A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3). CONCLUSIONS: A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2018;124:46-54. © 2017 American Cancer Society.

Trajectories of quality of life following breast cancer diagnosis.

PURPOSE: Although quality of life (QoL) improves over time for most breast cancer survivors (BCS), BCS may show different patterns of QoL. This study sought to identify distinct QoL trajectories among BCS and to examine characteristics associated with trajectory group membership. METHODS: BCS (N = 653) completed baseline assessments within 8 months of diagnosis. QoL was assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12, and 18 months later. Finite mixture modeling was used to determine QoL trajectories of the trial outcome index (TOI; a composite of physical well-being, functional well-being, and breast cancer-specific subscales) and emotional and social/family well-being subscales. Chi-square tests and F tests were used to examine group differences in demographic, cancer-related, and psychosocial variables. RESULTS: Unique trajectories were identified for all three subscales. Within each subscale, the majority of BCS had consistently medium or high QoL. The TOI analysis revealed only stable or improving groups, but the emotional and social/family subscales had groups that were stable, improved, or declined. Across all subscales, women in "consistently high" groups had the most favorable psychosocial characteristics. For the TOI and emotional subscales, psychosocial variables also differed significantly between women who started similarly but had differing trajectories. CONCLUSIONS: The majority of BCS report good QoL as they transition from treatment to survivorship. However, some women have persistently low QoL in each domain and some experience declines in emotional and/or social/family well-being. Psychosocial variables are consistently associated with improving and/or declining trajectories of physical/functional and emotional well-being.

Acupuncture for breast cancer-related lymphedema: a randomized controlled trial.

PURPOSE: Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL. METHODS: Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher's exact to determine the proportion of responders. RESULTS: Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between groups for arm circumference difference (0.38 cm greater reduction in AC vs. WL, 95% CI - 0.12 to 0.89, p = 0.14) or bioimpedance difference (1.06 greater reduction in AC vs. WL, 95% CI - 5.72 to 7.85, p = 0.8). There was also no difference in the proportion of responders: 17% AC versus 11% WL (6% difference, 95% CI - 10 to 22%, p = 0.5). No severe adverse events were reported. CONCLUSIONS: Our acupuncture protocol appeared to be safe and well tolerated. However, it did not significantly reduce BCRL in pretreated patients receiving concurrent lymphedema treatment. This regimen does not improve upon conventional lymphedema treatment for breast cancer survivors with persistent BCRL.