Older Breast Cancer Survivors: Perspectives on Healthcare Encounters and Unmet Needs

Breast cancer treatment advances have lengthened the survivorship period. Limited attention has focused on the myriad issues breast cancer survivors experience related to their cancer and other health conditions as they age. Focus groups, conducted Fall 2019 – Spring 2020 with a diverse sample of breast cancer survivors from the New York metropolitan region (N=28) explored survivors’ healthcare encounters and goals, quality of life, survivorship lifestyle, other health conditions and risks, e.g. emergence of COVID-19. Participants were 40-82 years old (57% were 56 or older); racially diverse (57% White, 18% Black, 14% Hispanic, 11% Bi-racial); 32% were married/partnered and 57% were parents. Mean diagnosis age was 51. Treatments received included lumpectomy (64%), chemotherapy (57%), radiation (46%), hormonal therapy (39%), and single/bilateral mastectomy (36%). Survivors expressed the importance of restoring normality in their life and the necessity to be pro-active in ensuring their health issues were addressed in medical encounters. Person-centered care and clinician engagement was valued, but not routinely experienced. Survivors evaluated treatment options not just on being cancer-free, but on how it would impact their whole life. They expressed concerns about the future and anxiety over long-term survival. Long term survivors, recipients of early experimental and/or extensive treatments, worried about an emergence of long-delayed adverse health consequences and complications managing other health issues in the future, particularly as they grew older. COVID-19 raised additional health concerns, particularly among those with high risk health conditions due to prior cancer treatments; various self-mandated protective activities were integrated into their self-care practices.

Cost–utility analysis of risk-reducing strategies to prevent breast and ovarian cancer in BRCA-mutation carriers in Switzerland

Objective We aimed to identify the most cost-effective of all prophylactic measures available in Switzerland for women not yet affected by breast and ovarian cancer who tested positive for a BRCA1/2 mutation. Methods Prophylactic bilateral mastectomy (PBM), salpingo-oophorectomy (PBSO), combined PBM&PBSO and chemoprevention (CP) initiated at age 40 years were compared with intensified surveillance (IS). A Markov model with a life-long time horizon was developed from the perspective of the Swiss healthcare system using mainly literature-derived data to evaluate costs, quality-adjusted life years (QALYs) and survival. Costs and QALYs were discounted by 3% per year. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. Results All prophylactic measures were found to be cost-saving with an increase in QALYs and life years (LYs) compared to IS. PBM&PBSO were found to be most cost-effective and dominated all other strategies in women with a BRCA1 or BRCA2 mutation. Lifetime costs averaged to 141,293 EUR and 14.5 QALYs per woman with a BRCA1 mutation under IS, versus 76,639 EUR and 19.2 QALYs for PBM&PBSO. Corresponding results for IS per woman with a BRCA2 mutation were 102,245 EUR and 15.5 QALYs, versus 60,770 EUR and 19.9 QALYs for PBM&PBSO. The results were found to be robust in sensitivity analysis; no change in the dominant strategy for either BRCA-mutation was observed. Conclusion All more invasive strategies were found to increase life expectancy and quality of life of women with a BRCA1 or BRCA2 mutation and were cost-saving for the Swiss healthcare system compared to IS.

P039 INTERCOSTAL HERNIA FOLLOWING DIEP RECONSTRUCTION: A CASE PRESENTATION

Aim Intercostal lung herniation is a rare clinical condition defined as the protrusion of lung parenchyma beyond the anatomic boundaries of the thoracic wall. Acquired lung hernias are typically occur secondary to trauma or are associated with severe pulmonary disease. We present a case of lung herniation following DIEP breast reconstruction which is the first reported case to date. Material and Methods 40-year-old woman with a history of bilateral mastectomy for breast cancer and subsequent delayed, bilateral DIEP breast reconstruction. She returned to the emergency department four days after her reconstruction with chest pain, shortness of breath and swelling of her chest. CT angiography of her chest demonstrated a focal protrusion of her right lung into her anterior chest wall (Figure 1). Thoracic surgery was consulted for repair which was achieved with a patch technique using Allomax dermal matrix. Results We describe the first reported intercostal lung hernia following DIEP breast reconstruction reported in scientific literature. Our patient had no history of trauma, thoracic surgery or pulmonary disease which are considered the greatest risk factors for acquired intercostal lung herniation. Much like abdominal wall hernias, protrusion of tissue through a small defect places tissue at risk for ischemia. Early recognition is thus essential to avoid tissue loss. Conclusions Intercostal lung hernia is an uncommon clinical entity that has not previously been described as a complication of DIEP breast reconstruction. Its development is associated with significant morbidity including flap loss in this case. Early recognition of this rare complication is essential to avoid more severe sequelae of tissue ischemia.

Pre-neoplastic stromal cells drive BRCA1-mediated breast tumorigenesis

Women with germline mutations in BRCA1 (BRCA1+/mut) have increased risk for developing hereditary breast cancer. Cancer initiation in BRCA1+/mut is associated with pre-malignant changes in the breast epithelium including altered differentiation, proliferative stress and genomic instability. However, the role of the epitheliumassociated stromal niche during BRCA1-driven tumor initiation remains unclear. Here, we show that the pre-malignant stromal niche promotes epithelial proliferation and BRCA1-driven cancer initiation in trans. Using single-cell RNAseq (scRNAseq) analysis of human pre-neoplastic BRCA1+/mut and control breast tissues, we show that stromal cells provide numerous pro-proliferative paracrine signals inducing epithelial proliferation. We identify a subpopulation of pre-cancer associated fibroblasts (pre-CAFs) that produces copious amounts of pro-tumorigenic factors including matrix metalloproteinase 3 (MMP3), and promotes BRCA1-driven tumorigenesis in vivo. Our gene-signature analysis and mathematical modeling of epithelial differentiation reveals that stromal-induced proliferation leads to the accumulation of luminal progenitor cells with altered differentiation, and thus contributes to increased breast cancer risk in BRCA1+/mut. Our results demonstrate how alterations in cell-cell communication can induce imbalances in epithelial homeostasis ultimately leading to cancer initiation. We anticipate our results to form the foundation for novel disease monitoring and therapeutic strategies to improve patient management in hereditary breast cancer. For example, pre-CAF specific proteins may serve as biomarkers for pre-cancerous disease initiation to inform whether radical bilateral mastectomy is needed. In addition, MMP inhibitors could be re-indicated for primary cancer prevention treatment in women with high-risk BRCA1 mutations.

Heterotopic Sex Cord-Stromal Proliferation: A Case Report

Introduction/Objective Sex cord-stromal cells at extraovarian sites are extremely rare and due to the low number of cases reported, the true incidence is unknown. We present the case of a patient with symptomatic uterine fibromas that had a benign extraovarian heterotopic sex cord-stromal proliferation. Methods/Case Report A 44-year-old female presented with pelvic pressure and discomfort. Past medical history is significant for breast cancer treated with bilateral mastectomy in 2019 followed by radiation treatments. The patient had no menses since January 2020 but had begun noticing spotting prior to the onset of her pelvic pressure and discomfort. Pelvic ultrasound revealed an enlarged uterus consistent with fibroids and a right adnexal mass. Endometrial biopsy following the ultrasound was normal. The patient desired definitive treatment and a total abdominal hysterectomy and bilateral salpingo-oophorectomy was subsequently performed. Gross examination of the surgical specimen revealed a fibroid uterus and normal appearing bilateral ovaries and fimbriated fallopian tubes. Histopathology showed a uterus with leiomyomata and serous cystadenofibromas in bilateral ovaries. The left fallopian tube fimbria showed a well-circumscribed proliferation of pale, ovoid cells in a microfollicular pattern. Rare cells with grooved nuclei were present. No significant atypia and no mitotic activity were identified. Immunohistochemical staining was positive for inhibin, WT-1, and vimentin. Negative stains include EMA, GATA-3, GCDFP 15, mammaglobin, chromogranin, and calretinin. Final diagnosis was determined to be benign fallopian tube with heterotopic sex cord-stromal proliferation. Results (if a Case Study enter NA) NA Conclusion This case highlights a rare, incidental finding. These lesions are postulated to represent non-neoplastic embryologic remnants. However, most heterotopic sex cord-stromal proliferations are found in fimbriae, which could suggest that they arise from heterotopic ovarian tissue exposed during ovulation. The incidence of these benign proliferations is expected to increase as routine sampling of adnexal structures is becoming more commonplace, which presents diagnostic challenges for pathologists.

Cytogenetic and molecular characterization of an SRY-negative 46, XX ovotesticular DSD

Introduction: Ovotesticular disorder of sex development is a rare condition by the concomitant presence of testicular and ovarian tissue, and usually presents genital ambiguity. Are chromosomally heterogeneous, and cytogenetic analyses is relevant. Objective: report on a patient from Manaus, Amazonas state with ovotesticular disorder of sex differentiation 46, XX and SRY-negative. Case report: Patient of 19 years, first child of non-consanguineous parents. At birth, the patient was diagnosed with genital ambiguity and, without early diagnosis, he was registered as being of the male sex. The patient underwent surgery to correct bilateral cryptorchidism, orchiopexy and colpectomy. During puberty, he developed female and male sexual characteristics. Endocrinological (normal total testosterone and estradiol as high follicle-stimulating hormone and luteinizing hormone), histopathological (right gonad, ovarian follicles and left gonads, atrophic testicles), karyotype (46, XX) and molecular (SRY-negative). Diagnosis of ovotesticular disorder of sex development was established. The patient chose to remain male and underwent bilateral mastectomy, vaginal colpectomy and bilateral gonadectomy. Currently, the patient receives hormonal replacement therapy, follow-up with a multi-professional approach and awaits masculinizing genitoplasty. Discussion: In diagnostic research, cytogenetic and molecular analysis are primary tools. For OT-DSD individuals with 46, XX, the female sex is suggested as the best sex option. Unlike the reported cases, the patient chose the male sex, since the sex at registration of birth was important in his choice. Conclusion: Cytogenetic and molecular analyses allowed us to assist in the etiological diagnosis of the patient with OT-DSD from Manaus. However, molecular analyses are necessary to elucidate the genes involved in the sexual determination of this patient.

Objective photographic assessments and comparisons of immediate bilateral breast reconstruction using deep inferior epigastric perforator flaps and implants

Background The increasing number of bilateral breast cancer patients has been accompanied by a growing need for bilateral mastectomy with immediate reconstruction. However, little research has investigated the complications and aesthetic outcomes related to bilateral reconstruction. Therefore, we analyzed retrospective data comparing the outcomes of bilateral reconstruction using deep inferior epigastric perforator (DIEP) flaps or implants.Methods This study included 52 patients (24 DIEP group and 28 implant group) who underwent bilateral mastectomy with immediate reconstruction between 2010 and 2020. Patient demographics, surgical characteristics, and complications were recorded. The difference between the left and right position of the nipple-areolar complex with respect to the sternal notch point at the clavicle was measured, and breast symmetry was evaluated.Results The average weight of breasts reconstructed with DIEP flaps (417.43±152.50 g) was higher than that of breasts with implants. The hospitalization period and operation time were significantly longer in the DIEP group. Early complications were significantly more common in the implant group (36.53%) than in the DIEP group. The angles between the nipples and the horizontal line were 1.09°±0.71° and 1.75°±1.45° in the DIEP and implant groups, respectively.Conclusions Although the surgical burden is lower, breast reconstruction using implants requires greater attention with respect to implant positioning, asymmetry, and complications than DIEP flap reconstruction. DIEP flap reconstruction has a prolonged operation time and a high risk of flap failure, but yields excellent cosmetic results and does not require intensive follow-up. Patients should be consulted to determine the most suitable option for them.

Post-Mastectomy Surgical Pocket Irrigation With Triple Antibiotic Solution vs Chlorhexidine Gluconate: A Randomized Controlled Trial Assessing Surgical Site Infections in Immediate Tissue Expander Breast Reconstruction

Background Post-mastectomy pocket irrigation solution choice is debated and primarily surgeon dependent. We compare triple antibiotic solution (TAS) to 0.05% chlorhexidine gluconate (CHG). Objectives The purpose of this study was to determine surgical site infection (SSI) rates after using TAS vs CHG for breast pocket irrigation in immediate tissue expander breast reconstruction. Methods A prospective, blinded, randomized controlled trial was performed in patients (18-81 years old) undergoing bilateral mastectomy with tissue expander (TE) reconstruction. In each patient, one mastectomy pocket was randomized to TAS and the other to CHG. Both the TE and the pocket were irrigated in the respective solution. The primary outcome was the incidence of surgical site infections (SSI). Secondary outcomes were rates of mastectomy flap necrosis, hematoma, and seroma. Results Eighty-eight patients undergoing bilateral immediate breast reconstruction were enrolled. Demographic and operative characteristics were equivalent as each patient served as their own control. Between the TAS and CHG groups, there was no difference in the incidence of SSI (5 [4.5%] vs 7 [8.0%], p = 0.35), including minor infections (2 [2.3%] vs 1 [1.1%], p = 0.56), major infections (2 [2.3%] vs 6 [6.8%], p = 0.15), and those resulting in explantation (2 [2.3%] vs 5 [4.5%], p = 0.25). There was also no difference in necrosis, hematoma, or seroma formation. No patients who developed SSI had radiation. Conclusions This study does not demonstrate a statistically significant difference in SSI between TAS and CHG irrigation, though TAS approached statistical significance for lower rates of infectious complications.