Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: a propensity-matched analysis.

BACKGROUND: There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer. METHODS: For this propensity-matched analysis, we used data from the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. We included data from women aged 70 years or older with surgically treated, American Joint Committee on Cancer (AJCC) Stage I-III invasive triple-negative breast cancer diagnosed from 2004 to 2014. Patients with T1aN0M0 disease and those with incomplete data on oestrogen receptor status, progesterone receptor status, or HER2 status were excluded. To reduce bias, patients were subdivided into three groups: those who were recommended chemotherapy but did not receive it; those who received chemotherapy; and those for whom chemotherapy was not recommended and not given. The primary outcome was overall survival. Multivariate Cox regression analysis and propensity score matching were done to minimise bias. FINDINGS: Between Jan 1, 2004, and Dec, 31, 2014, 16 062 women with triple-negative breast cancer in the database met the inclusion criteria for this analysis. Median follow-up was 38·3 months (IQR 20·7-46·1, range 0-138·0; 95% CI 37·8-38·7). Collectively, the 5-year overall survival estimate of the 16 062 patients in the study cohort was 62·3% (95% CI 59·7-64·4). 5-year estimated overall survival was 68·5% (95% CI 66·4-70·6) for patients receiving chemotherapy, 61·1% (59·0-63·2) for patients recommended but not given chemotherapy, and 53·7% (51·8-55·8) for patients not recommended chemotherapy and not given chemotherapy (pooled log rank p<0·0001). Multivariate Cox regression analysis of a propensity score-matched sample comparing those who received chemotherapy with those who were recommended but not given chemotherapy (n=1884 matched pairs) identified improved overall survival with chemotherapy (hazard ratio [HR] 0·69 [95% CI 0·60-0·80]; p<0·0001). After stratifying the propensity score matching sample, this benefit persisted for node-negative women (HR 0·80 [95% CI 0·66-0·97]; p=0·007), node-positive women (0·76 [0·64-0·91]; p=0·006), and those with a comorbidity score greater than 0 (HR 0·74 [95% CI 0·59-0·94]; p=0·013). INTERPRETATION: These data support consideration of chemotherapy in the treatment of women aged 70 years or older with triple-negative breast cancer. FUNDING: None.

Breast Cancer and the Obstetrician-Gynecologist: A Focus on Screening, Risk Assessment and Treatment of Survivors With Genitourinary Syndrome of Menopause.

Because of conflicting guidelines, providing appropriate breast cancer screening recommendations to our patients has become challenging. Given the high prevalence of genitourinary syndrome of menopause (GSM) overall, and among breast cancer survivors, and the understandable reluctance of physicians to prescribe effective hormonal treatments to survivors with this condition, addressing the needs of breast cancer survivors with bothersome GSM is both a common and controversial issue. In this review, we detail current breast cancer screening recommendations, breast cancer risk assessment, and management of GSM in breast cancer survivors.

Cost-effectiveness of surgeon performed intraoperative specimen ink in breast conservation surgery.

BACKGROUND: Re-excision rates after breast conservation surgery are reported to be 20%-40%. Inaccuracies with specimen orientation may affect margin assessment. This study examined whether the addition of surgeon performed intraoperative inking of the lumpectomy specimen after adoption of margin guidelines would be cost-effective. METHODS: A retrospective review of a prospective surgical database was performed from 2009 to 2017. Patients with initial lumpectomy and a preoperative diagnosis of invasive breast carcinoma or ductal carcinoma in situ (DCIS) were included. Re-excision rates and the surgical costs per 100 initial lumpectomies were compared across three periods: before margin guideline publication, after guideline adoption, and after the addition of intraoperative surgeon performed specimen inking. RESULTS: Four hundred initial lumpectomies were evaluated. Overall re-excision rate was 21% (n = 84). There was a nonsignificant reduction in re-excision rates after margin guidelines from 24% (n = 36) to 20% (n = 23) and to 19% (n = 25) after addition of intraoperative specimen ink. Re-excision rates were significantly lower for invasive cancer than for DCIS across three periods (20%, 15%, and 12% versus 37%, 33%, and 31%) (odds ratio 3.31, P = 0.007). The estimated cost of re-excision per 100 initial lumpectomies decreased after guidelines by 25% ($128,270) for invasive breast cancer and by 11% ($102,616) for DCIS. The addition of intraoperative specimen inking after margin guideline adoption resulted in further 17% cost savings ($66,692) for invasive breast cancer and 5% ($41,308) for DCIS. CONCLUSIONS: Surgeon performed intraoperative inking of the lumpectomy specimen after adoption of margin guidelines is a cost-effective technique in breast conservation surgery.

Evaluation of traditional targeted axillary dissection eligibility criteria for node-positive breast cancer after neoadjuvant chemotherapy in a prospective multicenter registry.

INTRODUCTION: Targeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. METHODS: Data was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. RESULTS: A total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00-11.93, p = 0.42; N stage: 95% CI 0.00-8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00-5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72-52.49, p = 0.13; radiotracer vs dual tracer 0.04-20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00-10.61, p = 0.38). CONCLUSIONS: TAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.

Efficacy of neoadjuvant cisplatin and oral capecitabine in triple-negative breast cancers: a pilot study.

Due to the lack of molecular targets, triple-negative breast cancers (TNBCs) typically represent a worse prognosis compared to their hormone-positive counterparts. While neoadjuvant chemotherapy has been used for breast cancers for a long time, there is no standard chemotherapy regimen for TNBCs. Cisplatin has generally been regarded as an effective chemotherapy agent against TNBCs. However, here we present a pilot study involving the use of cisplatin in combination with oral capecitabine in the neoadjuvant setting in 16 patients with TNBC. Twelve patients were African American and 4 patients were white. Six patients completed all 4 cycles of chemotherapy, 6 patients completed 3 cycles, and 4 patients completed 2 cycles. A complete clinical response was observed in 2 patients, and 10 patients achieved partial clinical response. One patient had progressive disease, and 3 patients were lost to follow-up or taken off study. Following chemotherapy, 12 patients underwent surgery (7 patients had breast conservation, and 5 patients had a mastectomy). Ten of the 12 patients who had surgery achieved a partial pathologic response and the other 2 patients had complete pathologic response. Grade 3 nausea, vomiting, and diarrhea occurred in 7 patients; 1 patient experienced dehydration and renal failure; and 5 patients had grade 1/2 hand-foot syndrome. There were no grade 4 or 5 toxicities. The response to cisplatin-capecitabine combination chemotherapy in the neoadjuvant setting was suboptimal compared to that with single-agent cisplatin in prior studies. The toxicity profile with this combination was also worse than that of cisplatin alone. Based on our findings, we do not recommend this combination regimen in the neoadjuvant setting for TNBCs. However, future studies analyzing the use of cisplatin with other combinations are warranted.

A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian and colorectal cancer susceptibility genes.

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences. METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019. RESULTS: In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). Compared to their prevalence in the overall sample, reclassification rates for Black individuals were higher (13.6% vs. 19.0%), whereas the rates for Asian individuals were lower (6.3% vs. 3.5%) and rates for White and Hispanic individuals were proportional. Two-year prevalence of VUS reclassification remained steady between 2014 and 2019. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals' clinical managements. CONCLUSIONS: The findings from this large multisite study suggest that VUS reclassification alters clinical management, has implications for precision cancer prevention, and highlights the need for implementing practices and solutions for efficiently returning reinterpreted genetic test results.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

The Effect of Insurance and Race on Breast Cancer Tumor Biology and Short-Term Outcomes.

To determine whether low-income status as demonstrated by insurance type has any association with aggressive tumor biology and breast cancer outcomes. Retrospective review of 535 women with new diagnosis of breast cancer from January 2009 to March 2013 was performed. There was no significant association between race and stage at diagnosis. Women with Medicaid/Charity coverage were diagnosed at more advanced stages, more likely to have triple-negative breast cancer (TNBC), and had longer time to treatment. Rate of TNBC was higher in black women and younger patients. There was no significant difference in breast cancer recurrence or survival by race, insurance type, age, or tumor biology. In multivariable analysis, only black race (P = 0.003) and Medicaid/Charity Insurance (P = 0.0008) were the most significant predictors of TNBC. Presentation of aggressive tumor biology and advanced stage is strongly associated with socioeconomic factors as reflected by Medicaid funding and lack of insurance.

Impact of chemotherapy on medium-term physical function and activity of older breast cancer survivors, and associated biomarkers.

OBJECTIVE: Chemotherapy is less often prescribed in older individuals due to concerns about post-treatment morbidity and quality of life. We evaluated the physical performance of breast cancer survivors treated with and without adjuvant chemotherapy. MATERIALS AND METHODS: We conducted a case-control study in 56 estrogen receptor positive breast cancer survivors (BCS) on adjuvant aromatase inhibitors 1-2years after definitive surgery. Cases had received adjuvant chemotherapy (n=27; age 70.5±3.6years) versus age-matched controls who had not (n=29; age 70.0±4.3years). Measures of grip strength, physical activity and performance, walking speed, fatigue, and self-reported physical function were collected. Biological correlates of inflammation, frailty and markers of DNA and RNA oxidation were compared. RESULTS: Grip strength (controls: 21±7.4 vs. CASES: 29.7±5.0kg, p=0.20), physical activity (5403±3204 vs. 6801±9320steps/day, p=0.45), physical performance (short physical performance battery score: 10.1±1.8 vs. 10.4±1.1, p=0.52) and long-distance walking speed (1.2±0.21 vs. 1.3±0.41m/s, p=0.17) were similar between the two groups. Self-reported physical function was marginally lower in cases than controls (controls: 72±24 vs. CASES: 57±34AU, p=0.07). Fatigue disruptiveness was not different between groups (controls: 11.1±13.0 vs. CASES: 15.7±16.2AU, p=0.24). Similarly, the inflammation, oxidation, and frailty markers did not present a significant difference between groups, except for vitamin D levels (p=0.04). CONCLUSION: Older women who received chemotherapy reported having slightly lower physical function, but a similar physical performance compared to women who did not. These data suggest that older BCS treated with chemotherapy recover to an extent similar to survivors who only received hormonal therapy.

Resolution of hypoalbuminemia after excision of malignant phyllodes tumor.

A 42-year-old woman presented with a rapidly growing tumor of the breast accompanied by anemia (7.4 g/dL), hypoalbuminemia (1.6 g/dL), and increased alkaline phosphatase (256 U/L). Magnetic resonance imaging of the breast demonstrated a heterogeneous mass composed of verrucous solid components with hemorrhagic areas. There was no evidence of cachexia, and the metastatic workup was negative. Final pathology revealed a 22-cm malignant phyllodes tumor. Hypoalbuminemia and alkaline phosphatase quickly resolved after surgical excision without any further treatment.

Evaluation of gastrointestinal stromal tumors for recurrence rates and patterns of long-term follow-up.

Retrospective chart review of 33 patients with gastrointestinal stromal tumors (GISTs) over the past 14 years was performed. Clinicopathologic variables were analyzed for patterns affecting tumor recurrence and need for long-term follow-up. No recurrence was found in the benign group and tumors <5 cm. In the malignant group, recurrence rate was 53 per cent with a mean follow-up of 34 months. Mean time to diagnosis of recurrence was 16 months. Eighty per cent of recurrences occurred within 2 years of surgical resection. Sixty per cent of recurrences were asymptomatic. Systematic follow-up consisted of physical examination and CT scans at 6-month intervals for 2 years after surgery. Time to diagnosis of a recurrence after surgery was 13 months for systematic follow-up and 18 months for sporadic follow-up. Mean survival was 24 months in both groups. Most recurrences occur within 2 years of surgical resection. Symptomatology does not provide early diagnosis. Patients who had systematic follow-up were diagnosed sooner with recurrence. Therefore, we recommend systematic follow-up after surgical resection of a malignant GIST to include physical examination and CT scan at 6-month intervals for up to 2 years after surgery with repeat CT scan at 3 years.