Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa).

PURPOSE: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. METHODS: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. RESULTS: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25). CONCLUSIONS: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Laparoscopic Management of a Heterotopic Pregnancy in the Tubal Stump.

STUDY OBJECTIVE: To demonstrate how a heterotopic tubal stump pregnancy can be safely managed with laparoscopy, preserving the intrauterine pregnancy. DESIGN: Stepwise demonstration of the technique by means of a video tutorial. SETTING: The management of pregnancies in the tubal stump after salpingectomy involves either a surgical intervention or systemic therapy. In case of a simultaneous intrauterine pregnancy, although the prognosis for the fetus remains good with live births in approximately 70% of the cases, the surgical management of the tubal stump pregnancy is challenging owing to the risk of bleeding from the uterine horn [1-5]. We present an effective and reproducible laparoscopic technique on the basis of a 31-year-old patient with 2 prior right fallopian tube pregnancies, which were later treated with salpingectomy. The patient is now presenting in the sixth week of gestation after transfer from 2 oocytes with a pregnancy in the tubal stump and a concomitant vital intrauterine pregnancy. INTERVENTIONS: The key steps of laparoscopic surgery include (1) continuous absorbable monofilament suture on the uterine horn around the tubal stump to achieve hemostasis and exposure of the proximal part of the tube, (2) removal of ectopic pregnancy, and (3) closure of the excision site with continuous absorbable polyfilament suture. The instillation of vasoconstrictive substances and the use of electrical coagulation should be avoided. CONCLUSION: The demonstrated laparoscopic technique is a feasible method of removal of a tubal stump pregnancy without interfering with the vital intrauterine pregnancy. The blood loss can be minimized, and laparotomy can be avoided.

Influences of adjuvant treatments in hormone receptor positive breast cancer on receptor conversion in recurrent breast cancer.

BACKGROUND: To examine influences on the receptor status of a local cohort of patients with recurrent breast cancer after primary diagnosis of hormone receptor positive breast cancer. METHODS: We retrospectively analyzed 2078 female patients with primary hormone receptor positive breast cancer treated at the university hospital of Wuerzburg between 2000 and 2013. Main focus was on discordance in receptor status in recurrent disease. RESULTS: 196 patients with the primary diagnosis of hormone receptor positive breast cancer developed recurrent disease. 29.1% of patients revealed discordance in estrogen receptor (ER), progesterone receptor (PgR) or HER2 receptor (ER+ to -: 33.3%; PgR+ to -: 59.6%; HER2+ to -: 8.8%; HER2- to +: 17.5%). Aggressive tumor biology such as low grading or involvement of axillary lymph nodes showed increased risk of receptor conversion in relapse. Premenopausal patients with adjuvant application of tamoxifen and the application of chemotherapy had a significantly lower risk for the development of ER negative recurrent disease. Receptor changes to ER and PgR negativity in recurrent disease showed a trend to worse overall survival (OS). CONCLUSIONS: Histological analysis of recurrent disease is indispensable, since one-third of patients with hormone receptor positive breast cancer develop change in the receptor status.

3D conformal radiotherapy is not associated with the long-term cardiac mortality in breast cancer patients: a retrospective cohort study in Germany (PASSOS-Heart Study).

PURPOSE: In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany. METHODS: A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account. RESULTS: We found no evidence for an effect of tumor laterality on mortality in irradiated patients (N = 9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64-1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85-1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk. CONCLUSIONS: Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.

Psycho-Oncological Care Provision in Highly Distressed Breast Cancer Patients.

Objective To evaluate the proportion of breast cancer (BC) patients with distress or psychological comorbidity as well as offer and use of psychological support in subgroups of BC patients with different extents of distress. Methods 456 patients with BC were evaluated at baseline (t1) and until 5 years after diagnosis (t4) at the BRENDA certified BC centers. Logistic regression was used to analyze if patients with distress at t1 received offers and actual psychological support more often than patients without distress at t1. Regression analyses were used to examine if acute, emerging or chronic disease was associated with higher rates of offer and use of psychotherapy as well as intake of psychotropic drugs. Results In 45% of BC patients psychological affection was detected at t4. The majority of patients with moderate or severe distress at t1 (77%) received the offer for psychological service, while 71% of those received the offer for support at t4. Patients, who were psychologically affected at t1, have not been offered psychological services more often than those without, but they significantly more often used services if offered. Especially patients with acute comorbidity received significantly more often an offer for psychotherapy compared to unimpaired patients, while those patients with emerging or chronic disease did not. 14% of BC patients took psychopharmaceuticals. This mainly concerns patients with chronic comorbidity. Conclusion Psychological services were offered to and used by a fair amount of BC patients. All subgroups of BC patients should be addressed, in order to improve the comprehensive supply with psychological services.

Does guideline-adherent therapy improve the outcome for early-onset breast cancer patients?

BACKGROUND AND OBJECTIVE: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients. METHODS: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines. RESULTS: Statistically significant differences between the two groups (<35 years, 36-55 years) were observed with regard to breast surgery (p = 0.002) and hormone therapy (p = 0.006). Both groups were treated identically in terms of guideline adherence concerning axillary dissection (p = 0.9), radiation therapy (p = 0.7) and chemotherapy (p = 0.556). Young breast cancer patients whose treatment adhered to guideline recommendations had increased RFS and OAS [RFS: p = 0.030, hazard ratio (HR) 2.95, 95% confidence interval (CI) 1.11-7.83; OAS: p < or = 0.001, HR 2.92, 95% CI 2.01-4.23]. CONCLUSION: Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients.

Comparison of early onset breast cancer patients to older premenopausal breast cancer patients.

BACKGROUND: The objective of this study was to show differences between breast cancer patients < or =35 and >35 years with regard to tumor characteristics and to present the patient-relevant outcomes overall survival (OAS) and recurrence-free survival (RFS). METHODS: We analyzed data from 119 women aged 35 years or younger with breast cancer and compared multiple parameters against breast cancer patients between 36 and 55 (n = 1,097), all pre-menopausal. Data were adjusted for tumor characteristics and therapy. RESULTS: There was no statistically significant difference in tumor size, axillary lymph node involvement, and histological subtypes. On the contrary, grading lymphovascular invasion and receptor negativity showed statistically significant differences. Unadjusted hazard ratio are 2.11 (1.32-3.39) (OAS) and 1.92 (1.35-2.73) (RFS). Multi-adjusted hazard ratio are 2.97 (1.70-5.18) (OAS) and 2.11 (1.42-3.13) (RFS). CONCLUSIONS: In conclusion, young breast cancer patients still have a poor prognosis. Even after adjustment of the data, OAS and RFS showed a worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement, and grading can therefore be not the explanation for the more aggressive disease progress within early onset breast cancer patients.

Effect of adjuvant radiotherapy in elderly patients with breast cancer.

BACKGROUND: Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival. METHODS: We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming. RESULTS: The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p<0.001) in RFS and tumor-associated OS stratified by GA-RT. The results remain the same after adjusting by adjuvant systemic treatment (AST) and comorbidity (ASA and NYHA). CONCLUSIONS: Patients aged 70 years and older suffering from low-risk early breast cancer with GA-BCS can avoid breast irradiation with <3% chance of relapse. In the case of higher-risk, breast irradiation should be used routinely following GA-BCS. As a side effect of these results, removing the entire breast of elderly low risk patients to spare them from breast irradiation seems to be not necessary.

The Role of Deconstructive Teaching in the Training of Laparoscopy.

BACKGROUND AND OBJECTIVES: Skills-lab training is crucial for the development of advanced laparoscopic skills. In this study, we examined whether a systematic deconstructive and comprehensive tutoring approach improves training results in laparoscopic suturing and intracorporeal knot tying. METHODS: Sixteen residents in obstetrics and gynecology participating in structured skills-lab laparoscopy training were randomized in 2 equal-sized groups receiving 1-on-1 tutoring either in the traditional method or according to the Peyton's 4-step approach, involving an additional training step, with the trainees instructing the tutor to perform the exercises. A validated assessment tool (revised Objective Structured Assessment of Technical Skills) and the number of completed square knots per training session and the mean time per knot were used to assess the efficacy of training in both groups. RESULTS: Trainees in Peyton's group achieved significantly higher revised Objective Structured Assessment of Technical Skills scores (28.6 vs 23.9 points; P = .05) and were able to improve their scores during autonomous training repetitions, in contrast to the trainees not in Peyton's group (difference +4.75 vs -4.29 points, P = .02). Additionally, they seemed to be able to perform a greater number of successful knots during the exercise and to complete each knot quicker with the later observations failing to reach the threshold of statistical significance. CONCLUSION: Peyton's 4-step approach seemed to be superior for teaching laparoscopic skills to obstetrics and gynecology residents in the skills-lab setting and can be therefore proposed for training curricula.

B2 Prognostic Score: External Validation of a Clinical Decision-making Tool for Metastatic Breast Cancer.

BACKGROUND: The B2 Prognostic Score (B2PS) is a clinical decision-making tool in metastatic breast cancer (MBC) that provides risk classification based on routine parameters. This study validates the B2PS in an independent series of MBC for the whole study group and for each intrinsic subtype. PATIENTS AND METHODS: We analyzed 641 metastasized patients, treated in 17 German certified breast cancer centers between 2001 and 2009. They were classified into low, intermediate, and high-risk groups according to B2PS. Overall survival (OS) curves for the various B2PS groups were compared with Kaplan-Meier method. RESULTS: According to the B2PS formula, 42.3% of patients were classified as low risk, 25.4% as intermediate risk and 32.3% as high risk. Intermediate- and high-risk patients had a statistically significant decreased OS compared with B2PS low-risk patients: (intermediate-risk: hazard ratio, 1.36; 95% confidence interval, 1.04-1.77; P = .023; high-risk: hazard ratio, 2.62; 95% confidence interval, 2.06-3.32; P < .001). The 5-year survival rates of low-, intermediate-, and high-risk patients were 41.3%, 26.9%, and 10.2%, respectively. The distribution of B2PS risk groups varied significantly within the intrinsic subtypes. For each intrinsic subtype, B2PS gives an additional risk classification. CONCLUSIONS: This study demonstrates the reproducibility of the B2PS based on routinely assessable parameters and confirms its prognostic value in an independent entire cohort of MBC as well as in the separate intrinsic subtypes. It therefore can help in counseling and individualizing the therapeutic regimens of those patients.

Vermilion Reconstruction with Genital Mucosa.

Functional and aesthetical reconstruction, especially of the upper lip after ablative tumor surgery, can be very challenging. The skin of the lip might be sufficiently reconstructed by transpositional flaps from the nasolabial or facial area. Large defects of the lip mucosa, including the vestibule, are even more challenging due to the fact that flaps from the inner lining of the oral cavity often lead to functional impairments. We present a case of multiple vermilion and skin resections of the upper lip. At the last step, we had to resect even the whole vermilion mucosa, including parts of the oral mucosa of the vestibule, leaving a bare orbicularis oris muscle. To reconstruct the mucosal layer, we used a mucosal graft from the labia minora and placed it on the compromised lip and the former transpositional flaps for the reconstructed skin of the upper lip with very good functional and aesthetic results.