Contemporary Review of the Management and Treatment of Young Breast Cancer Patients.

Approximately 11% of all new breast cancer cases annually are diagnosed in young women, and this continues to be the leading cause of death in women age 20 to 49. Young, premenopausal breast cancer patients present with more advanced stages and with a higher proportion of aggressive subtypes such as triple negative and HER2-enriched tumors. Recently, the United States Preventive Services Task Force (USPSTF) lowered the age threshold to initiate screening mammograms to age 40 to aid in earlier detection. Young age at diagnosis increases the likelihood for a pathogenic mutation, and genetic testing is recommended for all patients age 50 and younger. This population is often underrepresented in landmark clinical trials, and data is extrapolated for the treatment of young women with breast cancer. Despite there being no survival benefit to more extensive surgical treatments, such as mastectomy or contralateral prophylactic mastectomy, many patients opt against breast conservation. Young patients with breast cancer face issues related to treatment toxicities, potential overtreatment of their disease, mental health, sexual health, and fertility preservation. This unique population requires a multidisciplinary care team of physicians, surgeons, genetic counselors, fertility specialists, mental health professionals, physical therapists, and dieticians to provide individualized, comprehensive care. Our aim is to (1) provide a narrative review of retrospective studies, relevant society guidelines, and clinical trials focused on the contemporary treatment and management of YBC patients and (2) discuss important nuances in their care as a guide for members of their multidisciplinary treatment team.

Telehealth for Preoperative Evaluation of Patients With Breast Cancer During the COVID-19 Pandemic.

Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the initial treatment. Clinicodemographic characteristics were collected. Initial consultation types (office, telephone, or video) were categorized. Outcomes included time to consultation, surgeon touchpoints, time to surgery, surgery types, and reexcision rates. Continuous variables were compared using Mann-Whitney tests or t-tests, and categorical variables were compared using χ2 or Fisher's exact tests. Results Of 158 patients, 56% had initial telehealth consultations (21% telephone, 35% video) and 42% did not have a preoperative physical examination. Age, race/ethnicity, and stage distributions were similar between initial visit types. Median time to consultation was lower in the initial telehealth group than the office group (6 days vs 9 days, p = 0.01). Other outcomes (surgeon touchpoints, time to surgery, surgery type, reconstruction) were similar between visit types. We observed higher reexcision rates in patients with initial telehealth visits (20% telehealth vs 4% office, p = 0.01), but evaluation was limited by small numbers. The reexcision rate was 13% for patients with telehealth visits and no preoperative physical exam. Discussion During the initial pandemic period, the majority of new breast cancer patients had an initial telehealth surgical consultation. Office and telehealth consultation visits had comparable numbers of postconsultation surgeon touchpoints and most outcomes. Our findings suggest that telehealth consultations may be feasible for preoperative breast cancer consultations.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Care in the time of COVID-19: impact on the diagnosis and treatment of breast cancer in a large, integrated health care system.

PURPOSES: To delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20-5/17/20). METHODS: By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment characteristics of breast cancer patients diagnosed 3/17/20-5/17/20 to those diagnosed 3/17/19-5/17/2019. Outcomes included time from biopsy to consultation and treatment. Comparisons were made using Chi-square or Wilcoxon rank-sum tests. RESULTS: Fewer new breast cancers were diagnosed in 2020 during the SiP period than during a similar period in 2019 (n = 247 vs n = 703). A higher percentage presented with symptomatic disease in 2020 than 2019 (78% vs 37%, p < 0.001). Higher percentages of 2020 patients presented with grade 3 (37% vs 25%, p = 0.004) and triple-negative tumors (16% vs 10%, p = 0.04). A smaller percentage underwent surgery first in 2020 (71% vs 83%, p < 0.001) and a larger percentage had neoadjuvant chemotherapy (16% vs 11%, p < 0.001). Telehealth utilization increased from 0.8% in 2019 to 70.0% in 2020. Times to surgery and neoadjuvant chemotherapy were shorter in 2020 than 2019 (19 vs 26 days, p < 0.001, and 23 vs 28 days, p = 0.03, respectively). CONCLUSIONS: During SiP, fewer breast cancers were diagnosed than during a similar period in 2019, and a higher proportion presented with symptomatic disease. Early-stage breast cancer diagnoses decreased, while metastatic cancer diagnoses remained similar. Telehealth increased significantly, and times to treatment were shorter in 2020 than 2019. Our system continued to provide timely breast cancer treatment despite significant pandemic-driven disruption.

Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large, Integrated Health Care System is Feasible and Effective.

BACKGROUND: Intraoperative ultrasound (IUS) localization for breast cancer is a noninvasive localization technique. In 2015, an IUS program for breast-conserving surgery (BCS) was initiated in a large, integrated health care system. This study evaluated the clinical results of IUS implementation. METHODS: The study identified breast cancer patients with BCS from 1 January to 31 October 2015 and from 1 January to 31 October 2019. Clinicopathologic characteristics were collected, and localization types were categorized. Clinical outcomes were analyzed, including localization use, surgeon adoption of IUS, day-of-surgery intervals, and re-excision rates. Multivariate logistic regression analysis was performed to evaluate predictors of re-excision. RESULTS: The number of BCS procedures increased 23%, from 1815 procedures in 2015 to 2226 procedures in 2019. The IUS rate increased from 4% of lumpectomies (n = 79) in 2015 to 28% of lumpectomies (n = 632) in 2019 (p < 0.001). Surgeons using IUS increased from 6% (5 of 88 surgeons) in 2015 to 70% (42 of 60 surgeons) in 2019. In 2019, 76% of IUS surgeons performed at least 25% of lumpectomies with IUS. The mean time from admission to incision was shorter with IUS or seed localization than with wire localization (202 min with IUS, 201 with seed localization, 262 with wire localization in 2019; p < 0.001). The IUS re-excision rates were lower than for other localization techniques (13.6%, vs 19.6% for seed localization and 24.7% for wire localization in 2019; p = 0.006), and IUS predicted lower re-excision rates in a multivariable model (odds ratio [OR], 0.59). CONCLUSIONS: In a high-volume integrated health system, IUS was adopted for BCS by a majority of surgeons. The use of IUS decreased the time from admission to incision compared with wire localization, and decreased re-excision rates compared with other localization techniques.

Outpatient Mastectomy: Factors Influencing Patient Selection and Predictors of Return to Care.

BACKGROUND: After implementation of the Surgical Home Recovery (SHR) initiative for mastectomy within a large, integrated health delivery system, most patients are discharged on the day of the procedure. We sought to identify predictors of SHR and unplanned return to care (RTC). STUDY DESIGN: Mastectomy cases with and without reconstruction from October 2017 to August 2019 were analyzed. Patient characteristics, operative variables, and multimodal pain management were compared between admitted patients and SHR patients using logistic regression. We identified predictors of RTC in SHR patients, defined as 7-day readmission, reoperation, or emergency department visit. RESULTS: Of 2,648 mastectomies, 1,689 (64%) were outpatient procedures and the mean age of patients was 58.5 years. Predictors of SHR included perioperative IV acetaminophen (odds ratio [OR] 1.59; 95% CI, 1.28 to 1.97), perioperative opiates (OR 1.47; 95% CI, 1.06 to 2.02), and operation performed by a high-volume breast surgeon (OR 2.12; 95% CI, 1.42 to 3.18). Bilateral mastectomies (OR 0.70; 95% CI, 0.54 to 0.91), immediate reconstruction (OR 0.52; 95% CI, 0.39 to 0.70), and American Society of Anesthesiologists class 3 to 4 (OR 0.69; 95% CI, 0.54 to 0.87) decreased the odds of SHR. Of SHR patients, 111 of 1,689 patients (7%) experienced RTC. Patients with American Society of Anesthesiologists class 3 to 4 (OR 2.01; 95% CI, 1.29 to 3.14) and African American race (OR 2.30; 95% CI, 1.38 to 4.91) were more likely to RTC; receiving IV acetaminophen (OR 0.56; 95% CI, 0.35 to 0.88) and filling an opiate prescription (OR 0.51; 95% CI, 0.34 to 0.77) decreased the odds of RTC. CONCLUSIONS: Surgeon volume and multimodal pain medication increased the odds of SHR. Within the SHR group, American Society of Anesthesiologists Class 3 to 4 and African American patients increased the likelihood of RTC. This study helps optimize patient selection and perioperative practice for successful SHR.

Adoption of Opioid-Sparing and Non-Opioid Regimens After Breast Surgery in a Large, Integrated Health Care Delivery System.

BACKGROUND: Postoperative prescriptions have contributed to the opioid epidemic. In response, a large, integrated health care delivery system implemented initiatives to reduce outpatient opioid prescriptions. We evaluated the impact of these interventions on opioid-prescribing practices after breast surgery. METHODS: We examined postoperative prescribing practices before and after the 2016-2018 intervention period. Primary endpoints were the use of non-opioid regimens (NORs) and morphine milligram equivalents (MMEs) prescribed for postoperative pain management, while secondary endpoints were emergency department (ED) visits and readmissions within 7 days of surgery. RESULTS: In a survey of breast surgeons, 23% reported using NORs in 2017 versus 79% in 2019 (p < 0.001). Comparing 1917 breast operations from 2016 with 2166 operations from 2019, NORs increased from 9% in 2016 to 39% in 2019 (p < 0.001). Average discharge MMEs per operation decreased from 190 in 2016 to 106 in 2019 (p < 0.001). NOR failure (defined as an additional opioid prescription within 2 weeks of surgery) was < 1%. Significantly fewer postoperative ED visits occurred in the NOR group (1.9% NOR vs. 3.4% opioid regimen [OR]; p < 0.001). The 7-day readmission rates for NOR and OR patients were similar (0.49% NOR vs. 0.32% OR; p = 0.45). CONCLUSION: Between 2016 and 2019, breast surgeons in a large, integrated health care delivery system adopted NORs for nearly 40% of breast operations, and prescribed significantly fewer MMEs, with no increases in ED visits or readmissions for NOR patients. This suggests that initiatives to decrease opioid prescribing were successful and that a NOR for pain management after breast surgery is feasible.

Implementation of a Post-mastectomy Home Recovery Program in a Large, Integrated Health Care Delivery System.

BACKGROUND: The number of outpatient mastectomies, with and without reconstruction, has increased nationwide. In well-selected patient populations, same-day surgery for mastectomy is a safe option. A pilot project was initiated within the Kaiser Permanente Northern California healthcare system to facilitate surgical home recovery (SHR) for mastectomy patients, including patients undergoing implant-based reconstruction and bilateral mastectomies. METHODS: Surgical home recovery for mastectomy patients was implemented in October 2017. Specific measures in this initiative included management of patient expectations at initial consultation, education about postoperative home care, multimodality pain management, and timely post-discharge follow-up. All patients undergoing mastectomy were included, except those undergoing autologous tissue reconstructions. After a 6-month implementation period, rate of same day discharge over 6 months was compared before and after the SHR initiative. We also compared emergency department (ED) visits, reoperations, and readmissions within 7 days. RESULTS: Twenty-one medical centers participated in this initiative. Before implementing SHR, 164 of the 717 (23%) mastectomies were outpatient procedures, compared with 403 of the 663 (61%) after the implementation period. Although the rate of outpatient mastectomy increased significantly, there were no statistically significant differences in ED visits (5.2% vs. 5.1%, p = 0.98), reoperation (3.5% vs. 3.5%, p = 0.99), or readmission rates (1.4% vs. 2.7%, p = 0.08). CONCLUSIONS: By implementing standard expectations and sharing best practices, there was a significant increase in the rate of home recovery for mastectomy without compromising quality of patient care. The success of this pilot program supports SHR for mastectomy.

Modified Makuuchi incision for foregut procedures.

The Makuuchi or J incision completely exposes the liver and right-sided retroperitoneal organs. The modified Makuuchi incision also achieves a superb en face view of critical structures, including the hepatocaval junction and the esophageal hiatus, but does not divide the intercostal muscles, thus reducing muscle atrophy and postoperative pain. This incision also offers significant advantages over other incisions commonly used in foregut surgery. We describe herein the use of the modified Makuuchi incision for foregut procedures, with particular emphasis on strategic retractor placement.

Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients.

BACKGROUND: We prospectively assessed the incidence, risk factors, and costs associated with wound complications and lymphedema in melanoma patients undergoing inguinal lymph node dissection (ILND). MATERIALS AND METHODS: A total of 53 melanoma patients were accrued to 2 trials (June 2005 to July 2008) that included prospective evaluations of postoperative complications; 30-day wound complications included infection, seroma, and/or dehiscence. There were 20 patients who underwent limb volume measurement and completed a 19-item lymphedema symptom assessment questionnaire preoperatively and 3 months postoperatively. A multivariate analysis was performed to evaluate potential risk factors for complications. A microcosting analysis was also performed to evaluate the direct costs associated with wound complications. RESULTS: The 30-day wound complications were noted in 77.4% of patients. A BMI ≥ 30 (n = 28) increased the risk for wound complications (odds ratio [OR] = 11.4, 95% confidence interval [95%CI] 1.6-78.5, P = .01), while advanced nodal disease approached significance (OR = 9.0, 95%CI: 0.79-103.1, P = .08). Other risk factors, including diabetes, smoking, and the addition of a deep pelvic (iliac/obturator) dissection to ILND, were not significant. Of 20 patients, 9 (45%) developed limb volume change (LVC) ≥5% at 3 months, with associated mean symptom scores of 6.1 versus 4.6 for those without LVC. Costs for patients with wound complications were significantly higher than for those without wound complications. CONCLUSIONS: Postoperative wound complications and early onset lymphedema occur frequently following ILND for melanoma. Obesity is an adverse risk factor for 30-day wound complications that can significantly increase postoperative costs, as is likely the case for advanced disease. Risk reduction practices and novel treatment approaches are needed to reduce postoperative morbidity.

Rapamycin inhibits proliferation of estrogen-receptor-positive breast cancer cells.

BACKGROUND: Estrogen-receptor (ER)-positive breast cancers comprise the majority of sporadic breast cancers. Although 50% respond to antihormonal treatment, both primary and acquired resistance limit the utility of this therapy, and other agents are needed. Rapamycin, an inhibitor of the mammalian Target of Rapamycin (mTOR), possesses antitumor activity against many tumors including breast tumors, and particularly against ER-positive breast cancer cell lines. The sensitivity of these cells to rapamycin has been attributed to activation of the PI3K/Akt/mTOR pathway by nongenomic ER signaling. The purpose of this study was to evaluate the efficacy of rapamycin against ER-positive breast cancer, particularly under 17beta-estradiol (E2)-dependent conditions, and to investigate mechanisms of rapamycin-sensitivity in ER-positive cells. MATERIALS AND METHODS: Breast cancer cell lines were tested for sensitivity to rapamycin. Antiproliferative effects of rapamycin, alone and in combination with tamoxifen, were assessed under E2-dependent conditions. Western blot analysis was used to detect activation of mTOR by nongenomic ER signaling. RESULTS: Rapamycin effectively inhibits proliferation of the ER-positive MCF-7 cell line. In our system, this sensitivity is probably not due to nongenomic ER activation of the PI3K/Akt/mTOR pathway; rapid stimulation of mTOR occurred nonspecifically after medium replacement, and addition of E2 stimulated mTOR only after 1 h. Combining rapamycin and tamoxifen under E2-dependent conditions yielded additive/synergistic effects at effective concentrations. CONCLUSIONS: These results suggest that rapamycin may be an effective treatment for ER-positive breast cancer, either alone or in combination with tamoxifen, and also may be a potential therapy for tamoxifen-resistant cancers.

Links between CD147 function, glycosylation, and caveolin-1.

Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). l-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-catalyzed, beta1,6-branched, polylactosamine-type sugars, which account for its excess size. Therefore, CD147, which is itself elevated on invasive tumor cells, may make a major contribution to the abundance of beta1,6-branched polylactosamine sugars that appear on invasive tumor cells. It was shown previously that caveolin-1 associates with CD147, thus inhibiting CD147 self-aggregation and MMP induction; now we show that caveolin-1 associates with LG-CD147 and restricts the biosynthetic conversion of LG-CD147 to HG-CD147. In addition, HG-CD147 (but not LG-CD147) was preferentially captured as a multimer after treatment of cells with a homobifunctional cross-linking agent and was exclusively recognized by monoclonal antibody AAA6, a reagent that selectively recognizes self-associated CD147 and inhibits CD147-mediated MMP induction. In conclusion, we have 1) determined the biochemical basis for the unusual size variation in CD147, 2) established that CD147 is a major carrier of beta1,6-branched polylactosamine sugars on tumor cells, and 3) determined that caveolin-1 can inhibit the conversion of LG-CD147 to HG-CD147. Because it is HG-CD147 that self-aggregates and stimulates MMP induction, we now have a mechanism to explain how caveolin-1 inhibits these processes. These results help explain the previously established tumor suppressor functions of caveolin-1.