High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy.

BACKGROUND: Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS). METHODS: A tissue microarray of 47 primary high grade ovarian serous carcinomas and their recurrences was stained with primary antibodies directed against CXCR4 and pCXCR4. Beside the evaluation of the absolute tumor as well as TIC expression in primary and recurrent cancer biopsies the corresponding ratios for pCXCR4 and CXCR4 were generated and analyzed. The clinical endpoints were response to chemotherapy, OS as well as RFS. RESULTS: Patients with a high pCXCR4/CXCR4 TIC ratio in primary cancer biopsies showed a significant longer RFS during the first two years (p = 0.025). However, this effect was lost in the long-term analysis including a follow-up period of 5 years (p = 0.128). Interestingly, the Multivariate Cox regression analysis showed that a high pCXCR4/CXCR4 TIC ratio in primary cancer independently predicts longer RFS (HR 0.33; 95CI 0.13 - 0.81; p = 0.015). Furthermore a high dichotomized distribution of CXCR4 positive tumor expression in recurrent cancer biopsies showed a significantly longer 6-month RFS rate (p = 0.018) in comparison to patients with low CXCR4 positive tumor expression. However, this effect was not independent of known risk factors in a Multivariate Cox regression (HR 0.57; 95CI 0.24 - 1.33; p = 0.193). CONCLUSIONS: To the best of our knowledge we show for the first time that a high pCXCR4/CXCR4 TIC ratio in primary HGSOC biopsies is indicative for better RFS and response to chemotherapy. HIGHLIGHTS: • We observed a significant association between high pCXCR4/CXCR4 TIC ratio and better RFS in primary cancer biopsies, especially during the early postoperative follow-up and independent of known risk factors for recurrence. • High CXCR4 tumor expression in recurrent HGSOC biopsies might be indicative for sensitivity to chemotherapy. We found evidence that at the beginning of the disease (early follow-up) the role of the immune response seems to be the most crucial factor for progression. On the other hand in recurrent/progressive disease the biology of the tumor itself becomes more important for prognosis. • We explored for the first time the predictive and prognostic role of pCXCR4/CXCR4 TIC ratio in high-grade serous ovarian cancer.

Noncompliance with palliative systemic therapy in patients with distant metastatic breast cancer: a blind spot for oncologists?

PURPOSE: The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). METHODS: We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990-2011, age restriction: ≥ 85 years old). RESULTS: Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60 years at MBC diagnosis: 7.9%; 60-70 years: 13.2%; > 70 years: 15.6%). The rate of noncompliance was equally distributed over time (1990-1999: 12.2% vs. 2000-2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61 years, p = 0.015), had shorter metastatic disease survival (2 vs. 27 months, p < 0.001), had more often an aggressive tumor subtype (hormone-receptor negative carcinomas: 48.7% vs. 22.2%, p < 0.001), and had more often secondary MBC (95.0% vs. 73.6%, p = 0.001). CONCLUSIONS: Although the high rate of noncompliance in the subgroup of elderly patients was not unexpected, it is noticeable that even in the subgroup of patients who were younger than 60 years, approximately 8% also rejected any systemic therapy before a MBC-related death occurred This group of younger women rarely had any relevant comorbidities, were potential candidates for chemotherapy and knowingly declined the therapy options. Such patients are never or seldom seen by oncologists in their daily practice and therefore play a minor role in their personal perception of disease. Nevertheless, these under-reported cases make up a significant proportion of MBC.

Radiological Staging for Distant Metastases in Breast Cancer Patients with Confirmed Local and/or Locoregional Recurrence: How Useful are Current Guideline Recommendations?

BACKGROUND: Breast cancer patients with local and/or locoregional recurrence (LR) are at higher risk of developing distant metastases (DM) at a later time. Once LR has been confirmed, some international interdisciplinary guidelines recommend performing radiological examinations for DM to determine the course of further therapy (curative or palliative approach). This study analyzed the metastatic patterns of patients with LR with particular regard to the frequency of concurrent diagnosis of LR and DM; in other words: are radiological staging procedures actually justified for DM at the time of diagnosis of LR? METHODS: This study included all patients (n = 1368) who were diagnosed and treated for nonmetastatic breast cancer (Stage I-III) at the University Women's Hospital Basel, Switzerland between 1990 and 2009. RESULTS: In 137 patients, LR was diagnosed without a history of DM: in-breast/thoracic wall only, n = 90 (65.7%); involvement of axillary/supra-/infraclavicular lymph nodes, n = 47 (34.3%). DM was found at the time of diagnosis of LR in 44 patients (32.1%). Concurrent diagnosis of LR and DM occurred significantly more often in patients with lymph node recurrence compared with those with in-breast/chest wall recurrence (48.9% vs. 23.3%; p = 0.004). CONCLUSIONS: Approximately one-third of patients with a LR had synchronous DM at the time of their local/locoregional event. For this reason, routine systemic staging imaging at the time of LR should be an absolute requirement for planning further therapy. Confirmation of DM may spare the patients radical surgical interventions with questionable impact on survival in the face of an incurable disease.

Prospective Evaluation of Residual Breast Tissue After Skin- or Nipple-Sparing Mastectomy: Results of the SKINI-Trial.

OBJECTIVE: This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies. METHODS: Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease. RESULTS: Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies. CONCLUSIONS: Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909.

Long-Term Survival and Cure in Distant Metastatic Breast Cancer.

BACKGROUND: Previous data showed that distant metastatic breast cancer (MBC) might be curable in up to 3% of the cases in selected patients, mostly young, with good performance status and with low-volume metastatic disease, mainly by an aggressive multidisciplinary approach including aggressive combination chemotherapy regimens. These long-lasting responses question the belief that MBC is wholly incurable. This study evaluates the rate of long-term survivors and potentially cured patients in an unselected cohort of MBC patients. METHODS: We analyzed the data from 342 patients in whom distant MBC was diagnosed from 1990 to 2011. For this study, we defined a metastatic disease survival (MDS) of 9 years as inclusion criterion for long-term survivorship. RESULTS: Eighteen patients (5.3%) were long-term survivors (MDS: 126 months; range, 108-300 months). The rate of long-term survivors was equally distributed over time (1990-1999: 4.3% vs. 2000-2011: 5.9%, p = 0.63). Compared to patients who had a lower MDS, long-term survivors had significantly more often primary MBC (p = 0.005) and hormone receptor-positive carcinomas (p = 0.015). Age at MBC diagnosis, presence of visceral metastases, and limited number of metastatic sites at the time of MBC diagnosis appeared to have no significant impact on long-term survival. Long-term survival was not associated with the use of chemotherapy (50.0% vs. 65.7% in the control group, p = 0.21). Eight patients (2.3%) developed a complete remission and presented with no evidence of disease at the time of last follow-up (MDS: 234.5 months). CONCLUSION: Since long-term survivors in MBC comprise a relatively heterogeneous group, the factors that lead to the quite rare and felicitous case of long-term survival or even cure can hardly be evaluated systematically. Some patients may be considered cured of their disease. This fraction may be small, but the chance of survival, and even of cure, truly exists. Perhaps we must accept that the factors contributing to long-term survival remain an enigma. It appears, however, that aggressive chemotherapy is not the only key factor to long-term remission.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy.

BACKGROUND: Ovarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC. METHODS: A tissue microarray of biopsies of mostly high-grade primary serous OC and matched recurrences of 47 patients was stained with OX40. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance. RESULTS: Chemosensitivity correlated significantly with high OX40 positive immune cell density in primary cancer biopsies (p = 0.027). Furthermore patients with a higher OX40 expression in recurrent cancer biopsies showed a better outcome in recurrence free survival (RFS) (p = 0.017) and high OX40 expression was associated with chemosensitivity (p = 0.008). OX40 positive TICI in recurrent carcinomas significantly correlated with IL-17 positive tumor infiltrating immune cells in primary carcinomas (r s = 0.34; p = 0.023). Univariate cox regression analysis revealed a significant longer RFS and higher numbers of chemotherapy cycles for high OX40 tumor cell expression in recurrent cancer biopsies (HR 0.39, 95%CI 0.16-0.94, p = 0.036 and 1.28, 95%CI 1.05-1.55; p = 0.013). CONCLUSION: High OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy.

Use of Palliative Endocrine Therapy in Patients with Hormone Receptor-Positive Distant Metastatic Breast Cancer: How Often, How Effective, How Long?

BACKGROUND: This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. METHODS: An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. RESULTS: In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. CONCLUSIONS: Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET.

MPO density in primary cancer biopsies of ovarian carcinoma enhances the indicative value of IL-17 for chemosensitivity.

BACKGROUND: Cancer of the ovary is mostly discovered at a late stage and cannot be removed by surgery alone. Therefore surgery is usually followed by adjuvant chemotherapy. However, few reliable biomarkers exist to predict response to chemotherapy of ovarian cancer. Previously, we could demonstrate that IL-17 density is indicative for chemosensitivity. This study focuses on the predictive value of myeloperoxidase (MPO) concerning response to chemotherapy of ovarian cancer. METHODS: Biopsies of mostly high-grade primary serous ovarian carcinomas and their matched recurrences were stained with MPO after fixation in formalin and embedding in paraffin. For this staining the technique of tissue-microarray was used. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance as previously publised. Data for MPO could be analyzed in 92 biopsies. RESULTS: MPO and IL-17 positive immune cells correlated significantly in biopsies of primary and recurrent carcinomas (r s = 0.41; p = 0.004 and r s = 0.40; p = 0.007, respectively). MPO expression alone did not predict response to chemotherapy, but in multivariate cox regression analysis including age, residual disease, number of chemotherapy cycles, FIGO classification and combined categorized MPO and IL-17 cell densities of primary cancer biopsies, the combination of both immune markers was an independent prognostic factor for recurrence-free survival (p = 0.013, HR = .23, 95CI = 0.07-0.73). There was no chemoresistant patient in the subgroup of MPO + IL-17+, neither in primary nor in recurrent cancer biopsies. CONCLUSIONS: High MPO positive cell density enhances the indicative value of IL-17 for response to chemotherapy in ovarian carcinoma. Although, these results have to be validated in a larger cohort.

Breast cancer screening attendance in two Swiss regions dominated by opportunistic or organized screening.

BACKGROUND: In Switzerland, the French-speaking region has an organized breast cancer (BC) screening program; in the German-speaking region, only opportunistic screening until recently had been offered. We evaluated factors associated with attendance to breast cancer screening in these two regions. METHODS: We analyzed the data of 50-69 year-old women (n = 2769) from the Swiss Health Survey 2012. Factors of interest included education level, place of residence, nationality, marital status, smoking history, alcohol consumption, physical activity, diet, self-perceived health, history of chronic diseases and mental distress, visits to medical doctors and cervical and colorectal cancer screening. Outcome measures were dichotomized into ≤2 years since most recent mammography versus >2 years or never. RESULTS: In the German- and French-speaking regions, mammography attendance within the last two years was 34.9 % and 77.8 %, respectively. In the French region, moderate alcohol consumption (adjusted OR 2.01, 95 % CI 1.28-3.15) increased screening attendance. Compared to those with no visit to a physician during the recent year, women in both regions with such visits attended statistically significantly more often BC screening (1-5 times vs. no visit: German (adjusted OR 3.96, 95 % CI 2.58-6.09); French: OR 7.25, 95 % CI 4.04-13.01). Non-attendance to cervical screening had a negative effect in both the German (adjusted OR 0.44, 95 % CI 0.25-0.79) and the French region (adjusted OR 0.57, 95 % CI 0.35-0.91). The same was true for colorectal cancer screening (German (adjusted OR 0.66, 95 % CI 0.52-0.84); French: OR 0.52, 95 % CI 0.33-0.83). No other factor was associated with BC screening and none of the tests of interaction comparing the two regions revealed statistically significant results. CONCLUSION: The effect of socio-demographic characteristics, lifestyle, health factors and screening behavior other than mammography on non-attendance to BC screening did not differ between the two regions with mainly opportunistic and organized screening, respectively, and did not explain the large differences in attendance between regions. Other potential explanations such as public promotion of attendance for BC screening, physicians' recommendations regarding mammography participation or women's beliefs should be further investigated.

Unintended pregnancy during the first year after breast cancer diagnosis.

OBJECTIVES: Young women experience high levels of anxiety and distress during cancer diagnosis and therapy, and it can be devastating to become pregnant in this vulnerable state. Pregnancy during cancer treatment is strongly discouraged, as radiotherapy and chemotherapy administered during the first trimester of pregnancy result in increased congenital malformations. METHODS: In this study, we analysed an unselected, consecutive cohort of young breast cancer (BC) patients with regard to unintended pregnancy during the first year after BC diagnosis. We analysed all patients who were ≤40 years of age at initial BC diagnosis (n = 100, mean age at diagnosis: 35.9 years), according to data from the Basel Breast Cancer Database. The frequency of unintended pregnancy was assessed, and particular attention was given to patients' obstetric and reproductive history. RESULTS: Forty-two percent of the cohort (mean age 36.5 years) were identified as not at risk of unintended pregnancy during the first year after BC diagnosis. However, 58% of the cohort (mean age 35.6 years) were using an ineffective contraceptive method and thus were at risk of unintended pregnancy. The rate of unintended pregnancy was 3.5% in this group (two patients). Oncologists should be aware that the use of reliable contraception should be discussed before starting, and also during, adjuvant therapy. CONCLUSIONS: Oncologists should consider actively referring young BC patients to a gynaecologist to ensure proper contraceptive counselling.

Status of estrogen receptor 1 (ESR1) gene in mastopathy predicts subsequent development of breast cancer.

Mastopathy is a common disease of the breast likely associated with elevated estrogen levels and a putative risk factor for breast cancer. The role of estrogen receptor alpha (ESR1) in mastopathy has not been investigated previously. Here, we investigated the prevalence of ESR1 gene amplification in mastopathy and its prediction for breast cancer. Paraffin-embedded tissues from 58 women with invasive breast cancer were analyzed. For all women, tissues with mastopathy taken at least 1.5 years before first diagnosis of breast cancer were available. Tissue from 46 women with mastopathy without a diagnosis of breast carcinoma in the observed time frame (12-18 years) was used as control. Fluorescence in situ hybridization analysis revealed that ESR1 was amplified in nine of 58 (15.5 %) breast cancers. All ESR1-amplified breast cancers were strongly positive for estrogen receptor with ER immunohistochemistry. Interestingly, in women with ESR1 amplification in breast cancer, the amplification was detectable in mastopathic tissues prior to the first diagnosis of breast cancer but was absent in tissues from women with mastopathy who did not develop breast cancer. Our study suggests that ESR1 gene amplification is an early event in breast pathology and might be a helpful predictive marker to identify patients at high risk of developing breast cancer.

Epidemiology in ovarian carcinoma: Lessons from autopsy.

OBJECTIVE: We challenge epidemiologic knowledge regarding ovarian carcinoma (OC) by bridging the gap between clinical and autopsy data. METHODS: Autopsy reports, histological slides and clinical files from 660 patients in whom OC was diagnosed from 1975-2005 were studied (autopsy cohort, n=233; Clinical Cancer Registry from the local gyneco-oncologic center, n=427). RESULTS: Out of the autopsy cohort, we identified four distinct subgroups of patients: 1) OC was diagnosed before autopsy, n=156 (67.0%). 2) OC was an incidental finding, n=16 (6.8%). 3) The ovarian tumors were not primary OC but rather metastases from other primary tumors; this revised diagnosis was first made by using current histopathological knowledge/techniques, n=24 (10.3%). 4) Death was directly due to OC in its final stage and OC was first diagnosed by autopsy, n=37 (15.9%); when these cases were added to the Clinical Cancer Registry to an adjusted OC incidence model, the autopsy cases comprised 8.8% of the adjusted cohort and almost doubled the percentage of oldest patients (≥80 years at diagnosis) from 4.9% to 9.3% (p=0.013). CONCLUSIONS: Epidemiological data from the 1970s-1990s may overestimate true incidence because up to 10% of carcinomas in the ovary were not properly classified. Patients who were first diagnosed with OC by autopsy comprise a distinct subgroup. These are patients who have not been seen by specialized oncologists and thus play no role in their perception of the disease. Nevertheless, these cases have impact on prevalence and incidence data of OC and in an era of reduced autopsy rates will probably be overlooked.

Personal or first-degree family breast cancer history: which has higher impact on tumor detection and tumor size in breast cancer.

PURPOSE: A woman's risk of developing breast cancer (BC) is increased if she has a personal history (PH) or family history (FH) of the disease. We compared the impact of the two risk factors PH and FH on tumor detection and tumor size at diagnosis in a cohort of BC patients. METHODS: The study cohort comprised 1,037 invasive BC patients (≤70 years at diagnosis). From these, 92 patients (8.5%) had a positive PH and 151 patients (13.7%) had a positive first-degree FH. RESULTS: Compared to the tumors of patients without PH or FH, the lesions of patients who had a positive PH or a positive FH were more often found by radiologic breast examinations (RBE) (PH: 49.4%, FH: 43.4%, no PH/FH: 26.2%; both comparisons p < 0.001). In patients with a positive FH, the tumors were slightly less often found by RBE as in patients with a positive PH (p = 0.468). Patients with a positive PH or FH had smaller tumors compared with those without such a history (PH: 19.7 mm, FH: 19.6 mm, no PH/FH: 26.7 mm; p = 0.015/p < 0.001). The tumor sizes of patients with a positive PH were almost identical to those of patients with a positive FH (p = 0.999). CONCLUSIONS: In women with a positive FH or PH of BC, the increased awareness of BC risk led to the detection of smaller tumors compared to women who have not had this experience. However, comparison of the two risk factors showed that they had a similar impact on the RBE detection rate of BC lesions and that the tumor sizes were nearly identical.

Does prior hysteroscopy affect pregnancy outcome in primigravid infertile women?

OBJECTIVE: An increasing proportion of infertile women are subjected to hysteroscopy. The effect of hysteroscopy on the pregnancy rate in assisted reproduction has been demonstrated to be favorable, but cervical dilation in the course of hysteroscopy may have an adverse effect on pregnancy outcome. We sought to investigate the effect of hysteroscopy on the risk of early miscarriage, preterm delivery, low birthweight, and other complications of pregnancy. STUDY DESIGN: This was a longitudinal retrospective cohort study at a university hospital. Data of 654 first-time singleton pregnancies between January 1997 and March 2011 in women with primary infertility were retrieved from a prospective data collection. Four cohorts were constructed based on exposure to hysteroscopy and pregnancy outcome (early miscarriage vs live birth). The primary endpoint was the duration of pregnancy at 37 weeks. Pregnancy outcomes of 167 infertile patients exposed to cervical dilation and hysteroscopy were compared with those of 327 infertile women unexposed to hysteroscopy. RESULTS: The incidence of miscarriage, preterm birth, placenta previa, and premature rupture of membranes after maternal exposure to hysteroscopy was similar to that in women not exposed. CONCLUSION: Prior hysteroscopy in infertile women does not affect subsequent pregnancy outcome.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Breast cancer in women 80 years of age and older: a comprehensive analysis of an underreported entity.

BACKGROUND: Approximately 10% of breast cancer (BC) patients are over the age of 80. We present the first comprehensive review on this particular group of patients. PATIENTS AND METHODS: The treatments and disease courses of an unselected cohort of patients, whose age at first diagnosis was ≥ 80 years (n = 151), were compared to those of a group of women, who were aged 56-66 years (n = 372). RESULTS: The group of elderly patients had larger tumors at first diagnosis (25 mm vs. 18 mm, p < 0.001) and higher disease stages (I: 31.1% vs. 44.1%, IV: 11.9% vs. 5.4%; each p < 0.001). There were no significant differences between both groups in terms of histologic subtype, grading, hormonal receptor status and HER2 status. The tumors of older patients were more often detected by clinical examination (38.9% vs. 17.0%, p < 0.001) and less often by mammography/sonography (10.4% vs. 29.9%, p < 0.001). The rate of patients who died of BC were similar in both groups (21.2% vs. 21.5%, p = 1.00). In the patients who had no evidence of metastases and who opted for primary non-surgical management (n = 21), the tumor could be stabilized without considerable morbidity in only 42.9%. Persistence to adjuvant endocrine therapy was comparable (83.0% vs. 88.3%, p = 0.357). In the adjuvant as well as in the palliative settings, elderly patients received less chemotherapy than younger ones (adjuvant: 1.6% vs. 23.3%; palliative: 32.3% vs. 68.4%; each p < 0.001). For palliative treatments only, elderly patients received fewer treatment regimens (≥ 3 therapy lines: 16.0% vs. 54.9%, p < 0.001). In those patients who died of BC, elderly women had inferior overall (25 vs. 54.5 months, p < 0.001) as well as metastatic-disease survival (11.5 vs. 19 months, p = 0.062). CONCLUSION: It must be ensured that appropriate standard therapies should not be routinely withheld in older patients based on erroneous perceptions regarding the biological nature of BC in the elderly and lack of knowledge about available therapy regimens. Physicians should consider that preservation of current life circumstances and maintenance of quality of life are frequently more important than "classical" hard medical facts such as survival times.

Pyoderma gangrenosum of the vaginal vault after vaginal hysterectomy: only the correct diagnosis of a rare entity can prevent long-term morbidity.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease characterized by a wide variety in its clinical presentation and outcome. The etiology is unknown and the pathogenesis is poorly understood, but autoimmune mechanisms have been suggested. Gynecological reports about PG are particularly scarce. As gynecologists rarely encounter this disorder, the correct diagnosis can easily be missed. PATIENTS AND METHODS: This paper presents the first case to our knowledge of an idiopathic PG of the vaginal vault as a late complication after vaginal hysterectomy. CONCLUSION: We demonstrate how PG, a rare disorder, might be misdiagnosed and how only the correct diagnosis and treatment involving systemic glucocorticoids and wound care can spare the patients from long-term morbidity.