A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer.

PURPOSE: We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS: Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION: In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.

Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study.

PURPOSE: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort. METHODS: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data. RESULTS: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30). CONCLUSION: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.

Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial.

OBJECTIVE: HER2 mutations are associated with poor prognosis and are detected in 3-6% of cervical cancers. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, had activity in several HER2-mutant cancer types in the phase 2 SUMMIT basket study. We present updated and final results from the cervical cancer cohort of SUMMIT. METHODS: Eligible patients had HER2-mutant, metastatic or recurrent cervical cancer progressing after platinum-based treatment for advanced/recurrent disease. Patients received neratinib 240 mg/day; loperamide was mandatory during cycle 1. Confirmed objective response rate (ORR) was the primary endpoint. Duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), and safety were secondary endpoints. RESULTS: Twenty-two patients were enrolled; 18 (81.8%) had endocervical adenocarcinoma; median two prior systemic chemotherapy regimens (range 1-4). The most common HER2 variant was S310F/Y mutation (n = 13; 59.1%). Four patients had confirmed partial responses (ORR 18.2%; 95% CI 5.2-40.3); 6 had stable disease ≥16 weeks (CBR 45.5%; 95% CI 24.4-67.8). Median DoR was 7.6 months (95% CI 5.6-12.3). Median PFS was 5.1 months (95% CI 1.7-7.2). All-grade diarrhea (90.9%), nausea (54.5%), and constipation (54.5%) were the most common adverse events. Five patients (22.7%) reported grade 3 diarrhea. There were no grade 4 adverse events, no diarrhea-related treatment discontinuations, and two grade 5 adverse events, unrelated to neratinib: dyspnea (n = 1) and embolism (n = 1). CONCLUSIONS: Neratinib resulted in durable responses and disease control in patients with HER2-mutant metastatic/recurrent cervical cancer in SUMMIT. These findings support next-generation sequencing and tailored therapy for select patients with advanced cervical cancer. All responses occurred in patients with endocervical adenocarcinoma. Further assessment of neratinib in this setting is warranted. TRIAL REGISTRATION NUMBER: NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).

Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer.

PURPOSE OF REVIEW: In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. RECENT FINDINGS: There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.

Left atrial strain is reduced following trastuzumab in breast cancer patients.

BACKGROUND: The effect of trastuzumab therapy on left atrial (LA) function remains largely unknown. Our aim was to assess the changes in LA strain parameters longitudinally in patients treated with trastuzumab. METHODS: We retrospectively studied 170 patients with stage I-IV HER2+ breast cancer. All patients had baseline echocardiograms and repeat echocardiograms at 3 months and after 1 year. We measured LA strain at all three time points. Changes in LA strain and strain rate (sr) parameters were evaluated using repeated-measures mixed-effects models. The cohort was stratified according to development of cancer therapeutics-related cardiac dysfunction (CTRCD) during follow-up. RESULTS: The mean age was 52.7 ± 13.8 years, 25.3% had hypertension and 16.0% had metastatic disease. Multiple LA strain parameters (predicted delta value, [95%CI]) showed statistically significant declines in patients who developed CTRCD from baseline to the 3-month follow-up after multivariable adjustment; LA reservoir strain (LAεres ): -4.7%; [-8.1% to -1.3%], p = .007; LA conduit strain (LAεcon ): -2.8%; [-5.3% to -.4%], p = .021); and LAεres sr: -.2/s; [-.3/s to -.09/s], p < .001). In patients who did not develop CTRCD, LA strain parameters declined significantly but to a smaller degree than in the CTRCD group (LAεres : -1.7%; [-3.1% to -.3%], p = .020, LAεcon : -2.2%; [-3.3% to -1.1%], p < .001, and LA booster pump strain : -2.4%; [-3.5% to -1.4%], p < .001). LA strain rates did not decline significantly in the non-CTRCD group. CONCLUSION: Trastuzumab treatment was associated with declines in LA strain parameters in patients with breast cancer. The largest declines were observed in patients who developed CTRCD during treatment.

Clinical characteristics and outcomes in patients with metastatic breast cancer and pseudocirrhosis: a single center retrospective cohort study.

PURPOSE: Pseudocirrhosis is a term used to describe changes in hepatic contour that mimic cirrhosis radiographically, but lack the classic pathologic features of cirrhosis. This radiographic finding is frequently found in patients with metastatic breast cancer (MBC), but the risk factors and clinical consequences are poorly understood. METHODS: In this retrospective study, we identified patients with MBC and pseudocirrhosis who were treated at a single center from 2002 to 2021. We used chart extraction and radiology review to determine demographic characteristics, treatment history, imaging features, and complications of pseudocirrhosis. RESULTS: 120 patients with MBC and pseudocirrhosis were identified with the following BC subtypes: hormone receptor (HR) positive, HER2 negative (n = 99, 82.5%), HR+/HER2+ (n = 14, 11.7%), HR- /HER2+ (n = 3, 2.5%), and triple negative (TNBC; n = 4, 3.3%). All patients had liver metastases and 82.5% (n = 99) had > 15 liver lesions. Thirty-six patients (30%) presented with de novo metastatic disease. Median time from MBC diagnosis to pseudocirrhosis was 29.2 months. 50% of patients had stable or responding disease at the time of pseudocirrhosis diagnosis. Sequelae of pseudocirrhosis included radiographic ascites (n = 97, 80.8%), gastric/esophageal varices (n = 68, 56.7%), splenomegaly (n = 26, 21.7%), GI bleeding (n = 12, 10.0%), and hepatic encephalopathy (n = 11, 9.2%). Median survival was 7.9 months after pseudocirrhosis diagnosis. Radiographic ascites was associated with shorter survival compared to no radiographic ascites (42.8 vs. 76.2 months, p = < 0.001). CONCLUSIONS: This is the largest case series of patients with MBC and pseudocirrhosis. Nearly all patients had HR+ MBC and extensive liver metastases. Survival was short after pseudocirrhosis and prognosis worse with radiographic ascites.

Incorporation of Patient-Reported Outcomes Measurement Information System to assess quality of life among patients with breast cancer initiating care at an academic center.

BACKGROUND: Symptom burden and reduced quality of life (QOL) are considerable hurdles in oncology. The authors used the Patient-Reported Outcomes Measurement Information System (PROMIS), which assesses physical and psychosocial health, to establish a mean symptom burden, examine potential drivers, and characterize severe symptom burden in breast cancer patient subgroups with the goal of characterizing stage IV patient QOL and triaging patients to individualized supportive care services. METHODS: New patients at the University of California San Francisco Breast Care Center received questionnaires with 8 PROMIS domains: depression, anxiety, fatigue, sleep-related impairment, sleep disturbance, cognitive function, cognitive abilities, and physical function. PROMIS values were scored with the HealthMeasures service and were compared by age, cancer stage, and educational status. RESULTS: Stage IV patients with breast cancer (n = 169) reported higher depression and fatigue and worse cognitive function, cognitive abilities, and physical function than patients with stage 0 to III disease (n = 2577). As age increased, cognitive function impairment, depression, anxiety, and sleep-related symptoms decreased. More educated patients showed better physical function and less severe sleep disturbance and fatigue. Across all subgroups, patients with high anxiety had the greatest probability of worse symptom burden and function in other domains. CONCLUSIONS: This study provides an additional set of PROMIS population estimates across breast cancer demographic groups. The analysis of a large stage IV population reinforces that metastatic patients have impaired QOL across multiple domains. Because anxiety emerged as a potential driver of impaired QOL in other domains, earlier interventions to reduce anxiety could improve QOL overall. These analyses will help to determine appropriate thresholds of intervention. LAY SUMMARY: Patients receiving treatment for breast cancer can experience decreased quality of life. This study characterized differences in self-reported quality of life among patients of different ages, with different stages of cancer, and with different educational backgrounds. This study also examined the effect of decreased quality of life in one area (eg, anxiety) on another area (eg, difficulty in sleeping). Patients who were younger, had not attended college or technical school, or had stage IV cancer tended to have worse quality of life. Patients who had high levels of anxiety also tended to have high levels of impairment in other areas.

Use of 18F-FDG PET/CT as an Initial Staging Procedure for Stage II-III Breast Cancer: A Multicenter Value Analysis.

BACKGROUND: Metastatic staging imaging is not recommended for asymptomatic patients with stage I-II breast cancer. Greater distant metastatic disease risk may warrant baseline imaging in patients with stage II-III with high-risk biologic subtypes. NCCN Guidelines recommend considering CT of the chest, abdomen, and pelvis (CT CAP) and bone scan in appropriate patients. CT CAP and bone scan are considered standard of care (SoC), although PET/CT is a patient-centered alternative. METHODS: Data were available for 799 high-risk patients with clinical stage II-III disease who initiated screening for the I-SPY2 trial at 4 institutions. A total of 564 complete records were reviewed to compare PET/CT versus SoC. Costs were determined from the payer perspective using the national 2018 Medicare Physician Fee Schedule and representative reimbursements to the University of California, San Francisco (UCSF). Incremental cost-effectiveness ratio (ICER) measured cost of using PET/CT per percent of patients who avoided a false-positive (FP). RESULTS: The de novo metastatic disease rate was 4.6%. Imaging varied across the 4 institutions (P<.0001). The FP rate was higher using SoC versus PET/CT (22.1% vs 11.1%; P=.0009). Mean time between incidental finding on baseline imaging to FP determination was 10.8 days. Mean time from diagnosis to chemotherapy initiation was 44.3 days with SoC versus 37.5 days with PET/CT (P=.0001). Mean cost per patient was $1,132 (SoC) versus $1,477 (PET/CT) using the Medicare Physician Fee Schedule, with an ICER of $31. Using representative reimbursements to UCSF, mean cost per patient was $1,236 (SoC) versus $1,073 (PET/CT) for Medicare, and $3,083 (SoC) versus $1,656 (PET/CT) for a private payer, with ICERs of -$15 and -$130, respectively. CONCLUSIONS: Considerable variation exists in metastatic staging practices. PET/CT reduced FP risk by half and decreased workup of incidental findings, allowing for earlier treatment start. PET/CT may be cost-effective, and at one institution was shown to be cost-saving. Better alignment is needed between hospital pricing strategies and payer coverage policies to deliver high-value care.

Phase II study of irinotecan and temozolomide in breast cancer patients with progressing central nervous system disease.

PURPOSE: Breast cancer patients with progressing central nervous system (CNS) disease have limited treatment options. Few chemotherapy drugs with activity in breast cancer have well-documented CNS penetration. This phase 2 trial evaluated efficacy and safety of irinotecan 125 mg/m2 on days 1 and 15 with temozolomide 100 mg/m2 days 1-7 and days 15-21 of a 28 day cycle. METHODS: Breast cancer patients of any biological subtype and progressing brain metastases and/or leptomeningeal disease (LMD) were eligible. The primary endpoint was CNS response rate. Secondary endpoints were clinical benefit rate (CBR), time to progression (TTP), and overall survival (OS). Imaging studies evaluating intracranial and extracranial response were performed every 8 weeks. RESULTS: Thirty patients were evaluable for safety and efficacy. The most common hematologic and non-hematologic adverse events were neutropenia, and nausea and fatigue, respectively. There were two confirmed CNS partial responses (PR) and five patients with stable disease in the CNS ≥ 16 weeks, resulting in a 7% PR and 23% CBR. Median TTP was 2.3 months (range 13-444 days), and median OS from treatment initiation until death was 4.9 months (range 20-1023 days). Excluding patients with LMD, median TTP and OS were 3.1 and 5.6 months, respectively. Only one patient progressed systemically before CNS progression. CONCLUSIONS: The combination of irinotecan and temozolomide was well tolerated, demonstrated some clinical activity across multiple breast cancer subtypes with progressing CNS disease, and offers a reasonable option for patients who are not candidates for further radiation or clinical trials.

Registry study to assess hair loss prevention with the Penguin Cold Cap in breast cancer patients receiving chemotherapy.

PURPOSE: Chemotherapy-induced alopecia is a distressing side effect of cancer treatment. The aim of this registry study was to assess efficacy and tolerability of scalp hypothermia using Penguin Cold Caps (Penguin) in breast cancer patients. METHODS: Hair loss was assessed by patients using a 100-point Visual Analog Scale (VAS) and by physicians using the 5-point Dean Scale at baseline, every 3-4 weeks during chemotherapy, and at least 1 month after completion of chemotherapy. The primary efficacy endpoint for success was defined as ≤50% hair loss by patient report (VAS) at follow-up (FUP). Tolerability and satisfaction were assessed by patient report. RESULTS: 103 patients enrolled between 7/2010 and 6/2015; 97 are evaluable for the primary endpoint. Chemotherapy included docetaxel/cyclophosphamide (TC; n = 50) for 4-6 cycles every 3 weeks, weekly paclitaxel for 12 weeks then doxorubicin/cyclophosphamide (P/AC; n = 23) for 4 cycles every 2-3 weeks, AC then paclitaxel (AC/P; n = 10), docetaxel/carboplatin ± trastuzumab (TCH; n = 4) for 4-6 cycles every 3 weeks. Overall, 61% of patients successfully prevented CIA; impact was regimen specific: TCH 100%, TC × 4 84%, TC × 5-6 50%, P/AC 43%, AC/P 20%. The most common toxicity was headache, reported by 78.5% of patients with mean pain level 37/100. Satisfaction among those who completed scalp cooling (SC) and FUP ranged from 74 to 100%. All patients who completed SC/FUP recommended Penguin. CONCLUSIONS: Scalp hypothermia with Penguin is effective in reducing alopecia, particularly for non-anthracycline-based shorter regimens. Penguin was well tolerated and viewed favorably by most patients.

The DigniCap Scalp Cooling System and its use in the treatment of chemotherapy-induced alopecia.

Chemotherapy-induced alopecia remains an emotionally traumatic side effect for cancer patients that impacts the quality of life, may be protracted in duration and may influence treatment decisions. Scalp cooling has been shown to be effective in preventing chemotherapy-induced alopecia. The DigniCap Scalp Cooling System is designed to prevent hair loss by cooling the scalp to reduce the impact of chemotherapy on hair follicle cells. Recent studies have shown the safety, efficacy and low-grade toxicity of the DigniCap System with a 66.3% success rate in hair preservation (n = 106) relative to 0% in a nonrandomized control group according to a prospective pivotal study. Data also support improved quality of life in several domains. Two scalp cooling devices including the DigniCap are now US FDA cleared and can be offered as a part of standard of care.

Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

PURPOSE: To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). METHODS: This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were <43, had stage II-III BC, and received neoadjuvant therapy. Time to initiation of NAT was compared between women who underwent OS (STIM) and women who did not (control). Patient and tumor characteristics, as well as oncologic outcomes, were compared between STIM and control groups. RESULTS: 82 patients were included (34 STIM and 48 control). STIM patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from diagnosis to initiation of NAT was 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. CONCLUSION: Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

A randomized pilot trial of a positive affect skill intervention (lessons in linking affect and coping) for women with metastatic breast cancer.

BACKGROUND: We conducted a randomized pilot trial to examine the feasibility, acceptability, and preliminary efficacy of a 5 week positive affect skills intervention (LILAC: lessons in linking affect and coping) for women with metastatic breast cancer. Additionally, we examined whether online delivery of the intervention would offer comparable benefits as in-person delivery. METHODS: Women with metastatic breast cancer (N = 39) were randomized to an in-person intervention, online intervention, or in-person attention-matched control. Psychological well-being (depression [Center for Epidemiologic Studies Depression Scale], positive and negative affect [Differential Emotions Scale], cancer-specific quality of life [Multidimensional Quality of Life Scale-Cancer Version]), and positive coping (mindfulness, positive-affect skill use, and self-compassion [Self-Compassion Scale: Short-Form]) were assessed at baseline, 1 week post-intervention, and 1 month post-intervention follow-up. RESULTS: The LILAC intervention showed good feasibility, acceptability, and retention. Although the study was not adequately powered to detect between-group differences in change on preliminary efficacy outcomes, within-group comparisons revealed that LILAC participants (in-person and online combined) showed reductions in depression and negative affect by the 1 month follow-up (d = -0.81). Notably, LILAC participants fell below the clinical threshold for depression (Center for Epidemiologic Studies Depression Scale = 16) by the 1 month follow-up (t[17] = -2.22, P = .04, d = -0.52), whereas control participants did not differ from threshold (t[9] = 0.45, P = .66, d = 0.14). CONCLUSIONS: The LILAC intervention, regardless of delivery method, shows feasibility, acceptability, and preliminary efficacy for promoting psychological well-being in women with metastatic breast cancer. This research provides support for a larger randomized trial to test more definitively the potential benefits of LILAC. A strength of the LILAC intervention includes its innovative focus on positive affect. The efficacy of the online delivery suggests the potential for widespread Internet dissemination.

Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer.

Importance: Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited. Objectives: To evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life. Design, Setting, and Participants: A prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years. Exposures: Use of a scalp cooling system. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward. Main Outcomes and Measures: Self-estimated hair loss using the Dean scale was assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (≤50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months. Results: Among the 122 patients in the study, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%; 95% CI, 56.2%-75.4%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P < .001). Three of 5 quality-of-life measures were significantly better 1 month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27.3% (95% CI, 18.0%-36.6%) reported feeling less physically attractive compared with 56.3% (95% CI, 31.9%-80.6%) of patients in the control group (P = .02). Of the 106 patients in the scalp cooling group, 4 (3.8%) experienced the adverse event of mild headache and 3 (2.8%) discontinued scalp cooling due to feeling cold. Conclusions and Relevance: Among women undergoing non-anthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. Further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01831024.

A phase 1b study of the Akt-inhibitor MK-2206 in combination with weekly paclitaxel and trastuzumab in patients with advanced HER2-amplified solid tumor malignancies.

PURPOSE: Akt plays a key role in the aggressive pathogenesis of HER2+ malignancies, suggesting that Akt-inhibitors may be of therapeutic value in the treatment of HER2+ tumors. Preclinical studies demonstrate synergy between MK-2206, a selective allosteric Akt-inhibitor, with paclitaxel and trastuzumab. We aimed to evaluate the safety of this combination in patients with HER2+ malignancies. METHODS: We conducted a phase 1b study of weekly MK-2206 in combination with weekly paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg in patients with HER2+ malignancies. Dose escalation was performed using a modified toxicity probability interval method. Molecular profiling of archived tissue samples and limited PK analyses were performed. RESULTS: 16 patients with HER2+ tumors were enrolled (12 breast, 3 gastric, 1 esophageal). 81 and 75 % had received prior trastuzumab and taxane chemotherapy, respectively. MK-2206 135 mg/week was determined to be tolerable. Three dose-limiting toxicities were observed including two grade 3 rashes and 1 grade 3 neutropenia resulting in a > 7 day delay in treatment. Grade 3/4 adverse events include neutropenia (44 %), rash (13 %), peripheral neuropathy (6 %), and depression (6 %). 10 patients (63 %) demonstrated tumor response (3 complete, 7 partial). Median duration of response was 6 months. Exploratory analyses identified STARD3, TM7SF2, and G3BP1 as potential biomarkers of response. CONCLUSIONS: MK-2206 at a dose of 135 mg/week in combination with weekly paclitaxel and trastuzumab is safe and well tolerated, and is the recommended phase 2 dose for this combination. Preliminary data indicate significant clinical activity in patients with HER2+ tumors despite prior HER2-directed therapy.

Sexual Function in Cancer Survivors: Updates to the NCCN Guidelines for Survivorship.

By the year 2024, predictions estimate that there will be approximately 19 million cancer survivors in the United States, many of whom will experience the physical and/or psychosocial long-term effects of cancer and its treatment. Although sexual dysfunction is common among these individuals, causing increased distress and negatively impacting quality of life, this critical part of survivorship care is often underrecognized and undertreated. At the NCCN 21st Annual Conference, Drs. Melisko and Narus reviewed the sexual function recommendations in the NCCN Guidelines for Survivorship, offering practical strategies for assessing and managing both female and male sexual dysfunction.

SIS.NET: a randomized controlled trial evaluating a web-based system for symptom management after treatment of breast cancer.

BACKGROUND: As cancer survivorship increases, health care systems will be challenged to meet patient needs. With the limited availability of clinician time and resources, novel methods of using patient-reported outcomes may improve the quality and efficiency of follow-up care in patients with breast cancer. METHODS: The authors conducted a randomized trial in patients with TNM stage I to III breast cancer comparing standard care with SIS.NET (System for Individualized Survivorship Care, based on patient self-reported data, with review by Nurse practitioners, targeted Education, and Triage), a follow-up protocol including integration of online health questionnaires at 3-month intervals and the evaluation of self-reported symptoms monitored and addressed remotely by a nurse practitioner (NP). The primary endpoint was to quantify the time between symptom reporting and remote evaluation of symptoms. The secondary endpoint was to compare use of health care resources (breast cancer-related visits, total medical appointments, and laboratory and imaging studies) over an 18-month period. RESULTS: A total of 102 participants were enrolled; 2 patients were excluded due to cancer recurrence. In the SIS.NET arm, 74% of new or changed self-reported symptoms were reviewed by a NP in <3 days. SIS.NET patients reported more new or changed symptoms compared with standard care patients (7.36 vs 3.2; P = .0045). During the 18-month trial, there were no statistically significant differences noted between the SIS.NET and standard care arms with regard to oncology-related appointments (mean, 4.2 vs 4.1 appointments), number of physician visits (mean, 10.8 vs 9.6 visits), or medical tests (mean, 5.5 vs 5 tests). CONCLUSIONS: Integration of online health questionnaires with remote review by a NP facilitated symptom reporting and may provide a means of convenient symptom assessment, but it did not appear to reduce health care resource use.

Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer.

Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment.

Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer.

The impact of long-term tamoxifen therapy on ovarian function is not known. Understanding these effects will help reproductive-aged patients who desire future pregnancy make more informed decisions regarding their treatment. This is a retrospective cohort study in patients identified through the UCSF Cancer Registry and SPORE database. We enrolled women with a history of ductal carcinoma in situ (DCIS) or early stage invasive breast cancer who were premenopausal at diagnosis and did not receive chemotherapy. Menstrual histories were obtained through electronic and paper surveys. We compared the age of menopause onset and menstrual pattern changes between women who received tamoxifen (TAM) and those who did not receive tamoxifen (control). Neither group received chemotherapy. 250 subjects were included in this study (125 TAM, 125 control). Mean age of menopause onset was 51.0 for both the groups and was not associated with duration of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes, including amenorrhea, were more frequent in the TAM group than control group (any change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control, p < 0.001). Older age was associated with an increased risk of developing amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use in the absence of chemotherapy is not associated with an earlier age onset of menopause in patients with DCIS or invasive breast cancer and is unlikely to significantly accelerate ovarian aging.