Invasive ER Research Articles

EP484 - Triple negative male breast cancer: a case report

Abstract Background Male breast cancer (MBC) is a rare malignancy, may present at advanced disease stage. Triple negative breast cancer (TNBC) known to have the poorest prognosis of all other histological types of breast cancer. This paper presents a case of 71 years old gentleman diagnosed with TNBC. Materials and Methods A 71 years old male patient, presented with a right breast lump. Clinically he had a skin dent and a palpable 3cm lump underneath in the right breast axillary tail. Mammogram and breast US showed suspicious lesion in right breast axillary tail in addition to a suspicious lymph node in right axilla. Imaging guided core biopsies were taken from the breast and axillary abnormalities. The histology revealed grade1 invasive ductal carcinoma NST, ER 0, PR 0 and HER 2 negative. The Breast-Multidisciplinary Team meeting advised for mastectomy and axillary clearance, this has been performed. Result The postoperative Pathomorphology report revealed 23 mm triple negative invasive ductal carcinoma NST, grade 1with Ki67 10%, T2N1M0. The postoperative MDT recommended annual surveillance with mammogram for 5 years. Conclusions MBC is uncommon entity, accounting for < 1% of all breast cancer diagnosed in both genders and the MTNBC still is rarer, and mastectomy is the mainstay of surgical treatment in addition to chemotherapy and radiotherapy , however the later doesn’t affect the cause-specific survival rate.

Abstract GS01-02: Phase 3 study of neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by adjuvant pembrolizumab or placebo plus endocrine therapy for early-stage high-risk ER+/HER2− breast cancer: KEYNOTE-756

Abstract Background: KEYNOTE-756 (NCT03725059) is a global phase 3 study of neoadjuvant pembrolizumab or placebo + chemotherapy followed by adjuvant pembrolizumab or placebo + endocrine therapy (ET) in patients with early-stage high-risk ER+/HER2– breast cancer. Here, we report primary pCR results and residual cancer burden (RCB) outcomes. Methods: Eligible patients with T1c-2 (≥2 cm) cN1-2 or T3-4 cN0-2, centrally confirmed, grade 3, invasive ductal ER+/HER2− breast cancer were randomized 1:1 to receive neoadjuvant pembrolizumab 200 mg Q3W or placebo, both given with paclitaxel QW for 12 weeks, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide (neoadjuvant treatment). After definitive surgery (± radiation therapy), patients received pembrolizumab or placebo for 9 cycles + standard ET. Stratification factors include region (Eastern Europe, China, or Other), tumor PD-L1 status (CPS ≥1 [positive] vs CPS < 1 [negative]), nodal involvement (positive vs negative), ER positivity (≥10% vs < 10%) and anthracycline schedule (Q3W vs Q2W). Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS. Secondary endpoints include OS, pCR defined as ypT0 ypN0 and ypT0/Tis and safety. RCB was an exploratory endpoint and was assessed by a local pathologist at the time of surgery. RCB-0, -1, -2, and -3 denote increasingly larger residual disease. Results: 1278 patients were randomized to pembrolizumab + chemotherapy (n=635) or placebo + chemotherapy (n=643). At the final pCR analysis (May 25, 2023, first interim analysis data cutoff), median follow-up was 33.2 mo (range, 9.7-51.8). In the ITT population, pembrolizumab + chemotherapy showed a statistically significant improvement in pCR (ypT0/Tis ypN0) vs placebo + chemotherapy: 24.3% (95% CI, 21.0-27.8) vs 15.6% (95% CI, 12.8-18.6); estimated difference, 8.5 percentage points (95% CI, 4.2-12.8); P=0.00005; results were consistent for the secondary pCR definitions, ypT0 ypN0 (21.3% vs 12.8%) and ypT0/Tis (29.4% vs 18.2%). The benefit of pembrolizumab + chemotherapy on pCR was generally consistent in the prespecified subgroups. There were more patients with RCB-0 (24.7% vs. 15.6%) and RCB-1 (10.2% vs 8.1%) and fewer patients in the RCB-2 (40.8% vs. 45.3%) and RCB-3 categories (20.5% vs. 28.9%) in the pembrolizumab group versus the placebo group. In the neoadjuvant phase, grade ≥3 treatment-related AE rates were 52.5% with pembrolizumab + chemotherapy and 46.4% with placebo + chemotherapy, with 1 death in the pembrolizumab arm due to acute myocardial infarction. EFS results are still immature and continue to be evaluated. Conclusions: The addition of pembrolizumab to chemotherapy significantly increased the pCR rate and shifted RCB to lower residual disease categories in patients with early-stage high-risk ER+/HER2− breast cancer. Safety was consistent with the known profiles of each regimen. Citation Format: Fatima Cardoso, Joyce O'Shaughnessy, Heather McArthur, Peter Schmid, Javier Cortés, Nadia Harbeck, Melinda Telli, David Cescon, Peter A. Fasching, Zhimin Shao, Delphine Loirat, Yeon Hee Park, Manuel Gonzalez Fernandez, Gabor Rubovszky, Seock-Ah Im, Rina Hui, Toshimi Takano, Fabrice André, Hiroyuki Yasojima, Zhenzhen Liu, Yu Ding, Liyi Jia, Vassiliki Karantza, Konstantinos Tryfonidis, Aditya Bardia. Phase 3 study of neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by adjuvant pembrolizumab or placebo plus endocrine therapy for early-stage high-risk ER+/HER2− breast cancer: KEYNOTE-756 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-02.

Investigating the role of tumour-to-skin proximity in predicting nodal metastasis in breast cancer

BackgroundUnderstanding the factors influencing nodal status in breast cancer is vital for axillary staging, therapy, and patient survival. The nodal stage remains a crucial factor in prognostication indices. This study investigates the relationship between tumour-to-skin distance (in T1–T3 tumours where the skin is not clinically involved) and the risk of nodal metastasis.MethodsWe retrospectively reviewed data from 100 patients who underwent neoadjuvant chemotherapy (NACT). Besides patient demographics and tumour variables, a radiologist retrospectively reviewed pre-operative MRI to measure tumour-to-skin distance. R core packages were used for univariate (χ2 and T-Wilcoxon tests) and bivariate logistic regression statistical analysis.ResultsOf 95 analysable datasets, patients’ median age was 51 years (IQR: 42–61), 97% were symptomatic (rest screen detected), and the median tumour size was 43 mm (IQR, 26–52). On multivariate analysis, increasing invasive tumour size (p = 0.02), ER positivity (p = 0.007) and shorter tumour-to-skin distance (p = 0.05) correlated with nodal metastasis. HER2 was not included in multivariate analysis as there was no association with nodal status on univariate analysis. In node-positive tumours, as tumour size increased, the tumour-to-skin distance decreased (r = − 0.34, p = 0.026). In node-negative tumours, there was no correlation (r = + 0.18, p = 0.23).ConclusionThis study shows that non-locally advanced cancers closer to the skin (and consequent proximity to subdermal lymphatics) are associated with a greater risk of nodal metastasis. Pre-operative identification of those more likely to be node positive may suggest the need for a second-look USS since a higher nodal stage may lead to a change in therapeutic strategies, such as upfront systemic therapy, node marking, and axillary clearance without the need to return to theatre following sentinel node biopsy.

Concordant care in sentinel lymph node omission following Choosing Wisely® recommendations at a comprehensive cancer center

BackgroundIn 2016, the SSO and ABIM released a Choosing Wisely® guideline stating SLNB can be safely omitted in women ≥70 with HR ​+ ​HER-invasive breast cancer. No study evaluating concordance of care with this guideline has been performed within a comprehensive cancer center. MethodsFrom 2005 to 2020, there were 382 patients with cT1-2N0 invasive carcinoma ER+/PR+ and HER2-identified as having undergone SLNB. These patients were then separated into two groups; those in the pre-guideline concordance cohort (2005–2015) and those in the post-guideline concordance (2016–2020) cohort. Axillary management concordance was trended over time. Results382 patients from 2005 to 2020 with HR ​+ ​HER- IBC were identified. No difference was seen in SLNB pre-versus post-guidelines (p ​= ​0.35). Increased concordance was noted as age increased (p ​= ​0.0068) and adjuvant radiation therapy exclusion (p ​< ​0.0001) post-guideline release. Concordance improved over the years post-guideline release (R2 ​= ​0.45). ConclusionsSurgical guideline adoption occurs over time but may also be affected by outside decisions and factors. Further study into patterns of guideline adoption may facilitate improving adherence to guidelines.

Combined Oral Appliance Therapy and Adjunctive Minimally Invasive Er:YAG Laser Therapy for Complete Resolution of Severe Obstructive Sleep Apnea: A Clinical Case Report

Combined Oral Appliance Therapy and Adjunctive Minimally Invasive Er:YAG Laser Therapy for Complete Resolution of Severe Obstructive Sleep Apnea: A Clinical Case Report

Blood and urine biomarkers in invasive ductal breast cancer: Mass spectrometry applied to identify metabolic alterations

Specific classes of biomolecules may act as putative biomarkers in altered metabolic pathways related to breast cancer diagnosis, classification, and prognosis. This study aim an integrated metabolomic profiling of blood serum and urine from invasive ductal ER+ breast cancer cases (stage 2 and 3) and matched controls, using high performance liquid chromatography coupled with mass spectrometry. More than 400 metabolites were identified in both biofluids, either common (96 molecules) or specific molecules found only in blood serum or urine (109 and 136 molecules, respectively). Using the Metaboanalyst 5.0 software, by multi- and univariate analysis, the most significant biomolecules were selected for discrimination between the groups and for cancer staging.Polar molecules (amino acids, tryptophan metabolites, nucleosides) and lipids (free fatty acids, acyl carnitines, estrogen metabolites, choline-dependent glycerophospholipids and lysophosphatidyl derivatives, ceramides) were considered as significant, putative biomarkers of altered metabolic pathways. The biological significance of these findings will be amplified by further analysis of larger cohorts of patients and will be essential for the prospective evaluation and early diagnosis of breast cancer.

Genomic risk classification by the 70-gene signature and 21-gene assay in African American early-stage breast cancer patients.

e12568 Background: Genomic risk of recurrence assays provide prognostic information that aids treatment recommendations for patients with early breast cancer (EBC). The 70-gene signature (MammaPrint/MP) and the 21-gene assay (Oncotype DX/ODX) were both validated by large prospective, randomized clinical trials. Previous studies have directly compared the performance of these assays, with moderate discordance widely observed. Recent work showed poor prognostic performance of the ODX in African American (AA) EBC patients (Hoskins et al., 2021). Here, we compare the concordance of two genomic tests in an AA cohort. Methods: This retrospective analysis included a subset of self-reported AA patients from the prospective, observational PROMIS (n = 66, NCT01617954) and FLEX (n = 29, NCT03053193) registry trials, for whom both MP and ODX RS results were available. Patients were enrolled from 2012 to present. The PROMIS trial enrolled patients with intermediate ODX RS (18-30). MP results were obtained from standard testing performed centrally by Agendia, Inc. (Irvine, CA); ODX testing was performed by Genomic Health, Inc. (Redwood City, CA) and results were collected from patient case report forms. Results: AA patients (n = 95) included in this sub-analysis were 77% post-menopausal with a median age of 60 years. 28% of patients were aged ≤ 50 years. Of patients with metabolic data (n = 49), 63% were obese by body mass index (BMI &gt; 30), and 23% had type 2 diabetes mellitus (T2DM). Tumors were predominantly invasive ductal carcinoma (82%), T1 (73%), grade 2 (53%), ER+ (99%), HER2-negative (94%), lymph node-negative (86%), and MP High Risk (66%). By ODX clinical RS, 17% of tumors classified as low (0-17), 80% intermediate (18-30), and 3% high (31-100) risk. As expected, the large intermediate RS group reflects the inclusion of PROMIS patients. By TAILORx RS ranges, 76% of tumors were low risk (≤25). Of these, 61% (n = 44/72) classified as MP High Risk. Notably, 62% (n = 41/66) of tumors with TAILORx intermediate RS (11-25) were MP High Risk. Conclusions: The overall discordance between MP and ODX was 51% in these AA patients. Discordance was more frequent (61%) in ODX low risk (RS≤25) cases. Notably, of tumors with TAILORx intermediate RS (11-25), the majority (62%) classified as MP High Risk. Combined with previously published data in AA patients (Nunes et al., 2016), this results in a total of 57% (n = 52/91) of ODX low RS (≤25) tumors classified as MP High Risk. Recent data indicate that AA patients who receive a low (≤10 or ≤25) or intermediate RS (11-25) have higher recurrence rates and lower survival than White/Caucasian EBC patients with the same RS. In the current study, clinical outcomes are forthcoming; however, these data suggest the majority of AA patients are more likely to receive a MP High Risk result, which may capture the diversity of pathways driving tumor metastasis. Clinical trial information: NCT01617954, NCT03053193.

The clinical significance of oestrogen receptor expression in breast ductal carcinoma in situ

BackgroundOestrogen receptor (ER) in invasive breast cancer (BC) predicts response to endocrine therapy (ET) and provides prognostic value. In this study, we investigated the value of ER expression in ductal carcinoma in situ (DCIS) in terms of outcome and the impact on ET decision.MethodsIn total, 643 pure DCIS, diagnosed at Nottingham University Hospitals, were assessed for ER. Clinicopathological data were correlated against ER status, together with assessment of recurrence rate.ResultsER positivity was observed in 74% (475/643) of cases. ER positivity was associated with clinicopathological variables of good prognosis; however, outcome analysis revealed that ER status was not associated with local recurrence. In the intermediate- and high-grade ER-positive DCIS, 58% (11/19) and 63% (15/24) of the recurrences were invasive, respectively, comprising 7% and 6% of all ER-positive DCIS, respectively. Invasive recurrence in low-grade DCIS was infrequent (2%), and none of these patients died of BC. The ER status of the recurrent invasive tumours matched the primary DCIS ER status (94% in ipsilateral and 90% of contralateral recurrence).ConclusionThe strong correlation between DCIS and invasive recurrence ER status and the clinical impact of ET justify discussion of the use of ET in ER-positive DCIS treated by breast-conserving surgery. The excellent outcome of low-grade DCIS, which was almost always ER-positive, does not, in the opinion of authors, justify the use of risk-reducing ET. Therefore, the decision on ET for DCIS should be personalised and consider grade, ER status and other characteristics.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.

Estrogen Receptor Positive and Progesterone Receptor Negative Breast Cancer: the Role of Hormone Therapy.

ER+/PR- (estrogen receptor positive and progesterone receptor negative) tumors constitute only a small portion of the breast cancer population. Patients with ER+/PR- tumors, however, are characterized by worse survival compared to patients with ER+/PR+ (estrogen receptor positive and progesterone receptor positive) tumors. Controversy exists regarding the efficacy of hormone blocking therapy for patients with ER+/PR- tumors. The NCDB was queried between 2004 and 2015, and patients with invasive ER+/PR- tumors were identified. We employed univariate Cox proportional hazards to compare outcomes among patients that did or did not receive hormone blocking therapy. We identified 138,398 patients with invasive ER+/PR- tumors, 32,044 (23%) of whom did not receive hormone blocking therapy. The reasons for not receiving hormone blocking therapy included contraindications to treatment, death, patient refusal, and unknown. There were no significant differences in race, income quartile, or education quartile between patients who did and did not receive hormone blocking therapy. Patients who did not receive hormone blocking therapy underwent surgical assessment of the axilla more frequently than those who did receive hormone therapy. Our analysis demonstrated that hormone blocking therapy administration was associated with increased overall survival for up to 10years of follow up (HR: 0.58; 95% CI: 0.56-0.59, p < 0.001). Hormone blocking therapy may be associated with increased survival for breast cancer patients with ER+/PR- tumors. Although this benefit may last for years after completion of the course, up to 25% of patients do not receive this treatment. Strategies to increase the utilization and adherence to hormone blocking therapy regimens may improve patient survival outcomes.

The physiological aspect of thyroid-induced breast cancer: a case report

Background: Breast cancer has the second-highest prevalence of cancer in Indonesia. The aetiology of breast cancer involves endogenous sex hormone activity, estrogen. Besides, thyroid hormones have estrogen-like effects on breast tissue which are thought to play a role in the development of breast cancer. This case report aims to evaluate the physiological aspect of thyroid-induced breast cancer.Case Report: A 49-year-old Balinese woman came to the Primary Health Care with a history of uncontrolled hyperthyroidism for 5 years (2014-2019), complaining of a lump in her left breast. Open biopsy and immunohistochemistry were done (Grade III Invasive Carcinoma ER + 50%, Her + 2-3). Patients were diagnosed with stage 3B breast cancer and conservative treatment has been taken. The examination of TSH thyroid hormone was 0.204 µIU/mL (normal = 0.5 - 6 µIU/mL) and FT4 3.1 ng/dL (normal = 0.7-1.9 ng/dL).The primary management of patients was chemotherapy following by Modified Radical Mastectomy (MRM), hormone suppressant injection, as well as Herceptin. Those medications were effective in reducing the development of breast cancer through thyroid hormone pathway.Conclusion: Some studies showed hyperthyroidism increase the risk of breast cancer and that high thyroid levels can cause estrogen-like effects, trigger proliferation and angiogenesis by activating the same pathway as estrogen those are mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase ½ (ERK ½).

The Impact of Neoadjuvant Chemotherapy on Margin Re-excision in Breast-Conserving Surgery.

Neoadjuvant chemotherapy (NAC) can improve cosmesis by reducing resection volume. Breast-conserving surgery (BCS) aims to achieve clear excision margins while optimizing cosmesis. However, the influence of NAC on margin re-excision after BCS is unclear. This study examines the rate and determinants of margin re-excision in patients undergoing BCS following NAC in our institution. From 2011-2015, all patients treated with NAC prior to BCS were identified from a prospectively maintained database. Mann-Whitney and Fisher's exact test tests were used to compare variables in patients who did and did not require re-excision. Patients undergoing primary surgical treatment in 2015 comprised an unmatched comparison group. Of 211 patients treated with NAC, 69 initially underwent BCS. The re-excision rate was 32% (n = 22) compared to 17% in the primary operable group (38 of 221, p = 0.02). Re-excision rates were lowest in triple-negative and HER2+ tumors (0% and 10%, respectively). Lobular carcinoma and ER+ tumors had a significantly higher rate of re-excision (100% and 42%, respectively). Of 22 patients undergoing re-excision, 9 had further BCS and 13 had a mastectomy. The re-excision rate following NAC is almost twice that of patients who underwent primary operative management. Her2+ and triple-negative tumors have lower re-excision rates and may represent a selected cohort most suitable for BCS. Patients with invasive lobular carcinoma or ER+ disease have significantly higher rates of margin positivity, and these patients should be considered for a cavity shave during primary surgery to reduce the rates of re-excision.

Trastuzumab-Induced Severe Thrombocytopenia: A Case Report and Literature Review

We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×109/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.

Companion diagnosis by BRACAnalysis CDxTM and therapeutic experience of Olaparib for HER2-negative breast cancer

Abstract Background Olaparib has been approved for patients with germline BRCA1/2 mutations who have HER2 negative advanced / recurrent breast cancer, and BRACAnalysis diagnostic systemTM was started as a companion diagnostics, greatly advancing breast cancer treatment based on genetic diagnosis. We report the current status of companion diagnostics and the therapeutic experience of Olaparib. Methods Between July 2018 and February 2019, information on BRACAnalysis diagnostic systemTM and hereditary breast and ovarian cancer was provided to patients with HER2 negative advanced / recurrent breast cancer. Results Median age was 52 years. Twelve patients with breast cancer received companion diagnostics (5 advanced and 7 recurrent). Median treatment line at the time of the examination was 3, 8 cases were under chemotherapy. Deleterious mutations were detected in 1 case of BRCA1 (1651insG), 1 case of BRCA2 (4081insG) and 1 case of VUS (Q84E 478 C>G). A 53 - year - old female patient received Olaparib, with a strong family history of breast cancer (elder sister, maternal cousin and 2 maternal aunt). The pathological diagnosis was invasive ductal carcinoma, cT1cN3cM1 (OSS, LYM), Stage IV, ER (+), PgR (-), HER2 (-), and Ki-67 50 %. In 6th line chemotherapy, companion diagnostics revealed a germ line BRCA1 mutations. Subsequently, consciousness disturbance due to meningeal dissemination appeared, and commenced Olaparib on 7th line. Improvement of consciousness disturbance, decrease of tumor marker was observed, therapeutic effect was obtained, but her general condition deteriorated and died 3 months after meningeal dissemination diagnosis. Conclusion We experienced a patient in which Olaparib was effective for late line. While further development of precision medicine is expected, active companion diagnostics for eligible patients should be considered.

Preliminary outcome of non-ablative vaginal Erbium laser treatment for female stress and mixed urinary incontinence

ObjectiveThis prospective study presents a preliminary result to compare the clinical efficacy of patients with stress urinary incontinence and mixed urinary incontinence using minimal invasive Er:YAG vaginal laser. Materials and methodsA total of 20 patients were included, in which were 10 patients with SUI and 10 patients with MUI (stress and urge incontinence), and underwent a 2940 nm Er:YAG laser with a special SMOOTH mode in an outpatient office without anesthesia or postoperative medications. All patients completed two sessions of treatment with an interval time of 28 days. At three months after treatment, all patients were asked to a clinical visit for evaluate the clinical outcome by pre-treatment and post-treatment ICIQ-SF questionnaire. At pretreatment and 3 months after the completion of two therapy sessions, patients were asked to answer the ICIQ-SF questionnaire. The questionnaire consists of three scales for assessment of the treatment outcome of urinary incontinence as: no change (no change score), improvement (decrease score 1–5), and strong improvement (decrease score >5) for two groups of patients with SUI and MUI. All the results were compared by Student's t test with two way analysis of variance between the two groups. ResultsA total of 20 patients presented with SUI symptom relief and improvement with treatment satisfaction. All 10 patients with SUI reported improvement after vaginal laser treatment, 70% with marked improvement and 30% with improvement. All 10 patients with MUI also had improvement, 40% with marked improvement and 60% with improvement. There was no statistically significant difference in the treatment outcome between the two groups. ConclusionsVaginal Erbium laser produce provides vaginal collagen remodeling and synthesis that may repair and restore the pelvic floor function. Despite of sample limitation and short follow up, this treating procedure presented a good and a safe clinical outcome in patients with SUI and with MUI by assessment of ICIQ-SF questionnaire.

The Impact of Physician Productivity Metrics and Patient Tumor Biology on Receipt of RT in Elderly Patients with ER+ T1N0 Breast Cancer in a Tertiary Cancer Center

Among elderly patients with early-stage invasive ER+ breast cancer, multiple randomized clinical trials show adjuvant radiation (RT) after lumpectomy does not reduce rates of survival or mastectomy (CALGB 9343, PRIME II). However, in the US, rates of adjuvant RT in this population have decreased modestly, from 79% to 75% (Soulos, JCO 2012). To understand barriers and facilitators to de-implementation of RT in these patients, we hypothesized that the enactment of a “new start” productivity metric for radiation oncologists would increase the rate of RT receipt among patients who were seen in consult by a radiation oncologist and/or increase the use of partial breast irradiation (PBI). We reviewed patients at a tertiary care center over the age of 70 treated with lumpectomy for ER+ pT1N0 from 2015-2018. A productivity metric based on number of “new starts” for patients treated with RT was implemented in January 2017; patients were divided into pre- and post- metric implementation for primary analysis. Chi squared analyses were performed to evaluate patterns of RT receipt before and after the new start metric. Secondarily, chi squared analyses and binary multivariate logistic regression including age, HER2 status, multifocality, and LVI were performed on all patients referred for RT to investigate biologic predictors of receipt of RT. 501 patients met inclusion criteria, and 35% received adjuvant RT. 188 patients (37%) were not referred for RT consult and were excluded. Among 313 patients referred, the rate of RT was 55% prior to metric implementation versus 59% after (NS). There was no difference in RT use among high-volume or low-volume providers, or treatment at main campus versus the regional setting. There was no difference in use of PBI (20% vs 20%), hypofractionation (73% vs 71%), or conventional fractionation (1% vs 0%). Secondarily, univariate analysis of patients referred for RT trended toward LVI increasing rates of RT compared to no LVI (65% vs 53%, respectively, p=0.09); on multivariate analysis, only HER2 amplification was associated with receipt of RT (p=0.014). Review of physician notes indicated multifocality as a risk factor driving RT recommendation, but this was not consistent across providers. The implementation of productivity metrics did not significantly impact use of RT in a tertiary care center that is below the national average of RT use in elderly patients with early-stage ER+ breast cancer. Leadership priorities and centralized peer review may overshadow financial incentives in this context; these implementation strategies should be evaluated outside the tertiary setting. Secondarily, HER2 amplification, which was not available in the era of CALGB 9343, is infrequent (5%) but drives use of RT when present. With data suggesting favorable outcomes in early-stage ER+HER2+ patients, investigation of radiation de-escalation in this cohort is warranted.

Neuronatin is a modifier of estrogen receptor-positive breast cancer incidence and outcome.

Understanding the molecular mediators of breast cancer survival is critical for accurate disease prognosis and improving therapies. Here, we identified Neuronatin (NNAT) as a novel antiproliferative modifier of estrogen receptor-alpha (ER+) breast cancer. Genomic regions harboring breast cancer modifiers were identified by congenic mapping in a rat model of carcinogen-induced mammary cancer. Tumors from susceptible and resistant congenics were analyzed by RNAseq to identify candidate genes. Candidates were prioritized by correlation with outcome, using a consensus of three breast cancer patient cohorts. NNAT was transgenically expressed in ER+ breast cancer lines (T47D and ZR75), followed by transcriptomic and phenotypic characterization. We identified a region on rat chromosome 3 (142-178Mb) that modified mammary tumor incidence. RNAseq of the mammary tumors narrowed the candidate list to three differentially expressed genes: NNAT, SLC35C2, and FAM210B. NNAT mRNA and protein also correlated with survival in human breast cancer patients. Quantitative immunohistochemistry of NNAT protein revealed an inverse correlation with survival in a univariate analysis of patients with invasive ER+ breast cancer (training cohort: n = 444, HR = 0.62, p = 0.031; validation cohort: n = 430, HR = 0.48, p = 0.004). NNAT also held up as an independent predictor of survival after multivariable adjustment (HR = 0.64, p = 0.038). NNAT significantly reduced proliferation and migration of ER+ breast cancer cells, which coincided with altered expression of multiple related pathways. Collectively, these data implicate NNAT as a novel mediator of cell proliferation and migration, which correlates with decreased tumorigenic potential and prolonged patient survival.

Differences in clinicopatholgic characteristics and risk of mortality between the triple positive and ER+/PR+/HER2- breast cancer subtypes.

This study compared the demographic and clinicopathologic characteristics and risk of mortality between the triple positive (TP) and ER+/PR+/HER2- breast cancer subtypes. Cases of first primary female invasive TP and ER+/PR+/HER2- breast cancer were obtained from the California Cancer Registry. Logistic regression analysis was used to compare differences in factors associated with the TP versus the ER+/PR+/HER2- subtype. Cox regression was used to compute the adjusted risk of breast cancer-specific mortality of the TP versus ER+/PR+/HER2-. The odds of TP versus ER+/PR+/HER2- were higher with advanced stage, high grade, low SES, ≤ 45years of age (OR 1.48; CI 1.40-1.55), black (OR 1.11; CI 1.02-1.21), Asian/Pacific Islander (OR 1.15; CI 1.09-1.22), and uninsured (OR 1.42; CI 1.15-1.73). Unadjusted survival analysis indicated worse survival for the TP when compared with the ER+/PR+/HER2- subtype. However, adjusted risk of mortality for the TP subtype was not statistically significantly worse than the ER+/PR+/HER2- subtype. Young age, advanced stage and grade, low SES, black and API race, and lack of health insurance are more common in the TP subtype than in the ER+/PR+/HER2- subtype. However the risk of mortality between these two subtypes is similar.

PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2\u2212 Early Invasive Breast Cancer: a Molecular Imaging Study Using [18F]FDG PET/CT

PurposeIn PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of this study was to investigate the functional association of PIK3CA mutational status and tumor glycolysis in invasive ER+/HER2− early breast cancer.ProceduresThis institutional review board-approved retrospective study included a dataset of 67 ER+/HER2− early breast cancer patients. All patients underwent 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography ([18F]FDG PET/CT) and clinico-pathologic assessments as part of a prospective study. For this retrospective analysis, pyrosequencing was used to detect PIK3CA mutations of exons 4, 7, 9, and 20. Tumor glucose metabolism was assessed semi-quantitatively with [18F]FDG PET/CT using maximum standardized uptake values (SUVmax). SUVmax values were corrected for the partial volume effect, and metabolic tumor volume was calculated using the volume of interest automated lesion growing function 2D tumor size, i.e., maximum tumor diameter was assessed on concurrent pre-treatment contrast-enhanced magnetic resonance imaging.ResultsPIK3CA mutations were present in 45 % of all tumors. Mutations were associated with a small tumor diameter (p < 0.01) and with low nuclear grade (p = 0.04). Glycolytic activity was positively associated with nuclear grade (p = 0.01), proliferation (p = 0.002), regional lymph node metastasis (p = 0.015), and metabolic tumor volume (p = 0.001) but not with tumor size/T-stage. In invasive ductal carcinomas, median SUVmax was increased in PIK3CA-mutated compared to wild-type tumors; however, this increase did not reach statistical significance (p = 0.05). Multivariate analysis of invasive ductal carcinomas revealed [18F]FDG uptake to be independently associated with PIK3CA status (p = 0.002) and nuclear tumor grade (p = 0.046). Size, volume, and regional nodal status had no influence on glycolytic activity. PIK3CA mutational status did not influence glycolytic metabolism in lobular carcinomas. Glycolytic activity and PIK3CA mutational status had no significant influence on recurrence-free survival or disease-specific survival.ConclusionsIn ER+/HER2− invasive ductal carcinomas of the breast, glucose uptake is independently associated with PIK3CA mutations. Initial data suggest that [18F]FDG uptake reflects complex genomic alterations and may have the potential to be used as candidate biomarker for monitoring therapeutic response and resistance mechanisms in emerging therapies that target the PI3K/AKT/mTOR pathway.

Prognostic Value of the Progesterone Receptor by Subtype in Patients with Estrogen Receptor-Positive, HER-2 Negative Breast Cancer.

In estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative breast cancers, the progesterone receptor (PR) is an independent prognostic marker. Little is known about the prognostic value of PR by tumor grade. We assessed this in two independent datasets. Women with primary operable, invasive ER+ HER-2 negative breast cancer diagnosed between 2000 and 2012, treated at University Hospitals Leuven, were included. We assessed the association of PR status and subtype (grade 1-2 vs. grade 3) with distant recurrence-free interval (DRFI) and breast cancer-specific survival. The interaction between PR status and subtype was investigated, and associations of PR status by subtype were calculated. The BIG 1-98 data set was used for validation. In total, 4,228 patients from Leuven and 5,419 from BIG 1-98 were analyzed. In the Leuven cohort, the adjusted hazard ratio (HR) of PR-positive versus PR-negative tumors for DRFI was 0.66 (95% confidence interval [CI], 0.50-0.89). For the interaction with subtype (p = .34), the HR of PR status was 0.79 (95% CI, 0.61-1.01) in luminal A-like and 0.59 (95% CI, 0.46-0.76) in luminal B-like tumors. In luminal A-like tumors, observed 5-year cumulative incidences of distant recurrence were 4.1% for PR-negative and 2.8% for PR-positive tumors, and in luminal B-like 18.7% and 9.2%, respectively. In the BIG 1-98 cohort, similar results were observed; for the interaction with subtype (p = .12), the adjusted HR of PR status for DRFI was 0.88 (95% CI, 0.57-1.35) in luminal A-like and 0.58 (95% CI, 0.43-0.77) in luminal B-like tumors. Observed 5-year cumulative incidences were similar. PR positivity may be more protective against metastatic relapse in luminal B-like versus luminal A-like breast cancer, but no strong conclusions can be made. In absolute risk, results suggest an absent PR is clinically more important in high compared with low proliferative ER+ HER-2 negative tumors. An absent progesterone receptor (PR) predicts a worse outcome in women treated for an estrogen receptor-positive, human epidermal growth factor receptor 2 negative breast cancer. As low proliferative tumors lacking PR are now also classified high risk, the prognostic value of PR across risk groups was studied. Despite a negative test for interaction of the prognostic value of PR by tumor grade, the magnitude of an absent PR on breast cancer relapse is much larger in high than in low proliferative breast cancers.