Archives of Breast Cancer
Volume:9 Issue: 4, Nov 2022

During the COVID-19 pandemic, health resources were stretched, access was impacted by lockdowns and there were concerns about exposure to the virus during visits to hospitals. The purpose of this study was to examine how breast cancer treatments (presentation, surgery, radiotherapy, chemotherapy and/or endocrine therapy) changed or were adapted during the early phase of the pandemic.

A systematic review was conducted using PRISMA guidance. Eligible studies presented original data reporting changes to early breast cancer treatment by comparing ‘pandemic’ treatment to a ‘pre-pandemic’ cohort or to ‘ideal’ treatment of individual cases. Data were extracted into evidence tables and narrative synthesis was used to analyze results.

Fifteen studies with paired design were eligible. These reported outcomes for 6,353 people treated for early breast cancer (January 2020–June 2021). All studies reported some change to treatment due to the pandemic. The nature of reported changes was inconsistent. Changes included: more advanced tumours at presentation compared to pre-pandemic, an increase in breast conserving surgery; an increase in simple mastectomy (without breast reconstruction); a trend towards increased wait times, delays to start of treatment, shorter post-operative hospital stay and hypofractionation or omission of radiotherapy. Centres used more or less neoadjuvant chemotherapy or endocrine therapy.

In the early stage of the pandemic, fewer early-stage breast cancer cases were treated at many centres. Treatment for breast cancer was impacted and various local solutions were developed. These included less complicated breast surgery, increased use of neoadjuvant therapy, and changes to radiotherapy regimens. Surgery was frequently delayed and breast reconstruction was often unavailable. These results have implications for breast cancer services during the pandemic recovery as a ‘catch-up’ increase in cancer diagnoses is expected. Women may wish to access breast reconstruction, unavailable due to COVID-19. The impact of changes to treatment on long-term quality of life should be evaluated.

Quinacrine (QC), an attractive anticancer drug, has been forwarded for clinical evaluation in various cancer types due to its tremendous safety data accumulated since World War II. Its shotgun nature makes it unmissable as a chemotherapy drug that traps and activates multiple pathways.

Recently, QC has been shown to block malignancy by affecting pathways, including RHO signaling, G1/S arrest, ROS emission, and cell death through autophagy. In this review, we have extensively studied QC as an anticancer agent that affects various signaling pathways. We have documented activity via WNT, NOTCH, HEDGEHOG, MAPK, EGFR, P53, RHO, AKT, NF-k and TGF pathways and reformed the already established mode of action of QC.

QC’s effects on multiple key signaling pathways, implicated in the malignant progression of numerous cancer types, make it an exciting candidate as a chemotherapeutic agent for new combination treatments and therapies.

Transcription factor GATA-3 is a relatively new and specific biomarker for breast carcinoma that regulates luminal cell differentiation. However, further studies that elucidate its role and diagnostic utility in primary breast cancer are required. Therefore, this study was conducted to assess GATA-3 expression in primary breast carcinoma and determine its association with various known prognostic and predictive factors of breast carcinoma.

This was a cross-sectional, observational study where 110 breast carcinoma cases were examined histologically on H&E stained slides for routine parameters such as tumor morphological type and histologic grade. ER/PR/Her-2- neu/ki67 and GATA-3 expression was determined using immunohistochemistry. All cases were assessed to determine the association of GATA-3 with different established clinicopathological characteristics in breast cancer such as patient age, axillary lymph node status, tumor grade, lymphovascular invasion, molecular subtype, etc. The results were statistically analyzed and P value < 0.05 was considered to be significant.

Overall, 97 cases (88.1%) expressed GATA-3 which was significantly associated with most of the established clinico-pathological parameters like family history of breast cancer, tumor size and histology grade, lymph node and margin status, presence of lymphovascular invasion and carcinoma in-situ component. GATA-3 expression was also significantly associated with ER/PR/HER2neu/ki67 expression.

GATA-3 expression is significantly associated with the different established prognostic parameters of breast cancer. Therefore, it may be considered as a relevant marker in primary breast carcinoma more routinely. Further studies of GATA-3 in breast cancer may refine prognostic models, predict clinical outcomes, and modify treatment guidelines in future.

In partial-breast irradiation (PBI), an accurate target volume delineation based on the lumpectomy cavity (LC) has been reported to remain difficult due to uncertain LC identification. However, the impact of accurate LC delineation on the planning target volume (PTV) has not been investigated.

Between September 2018 and April 2020, 159 patients receiving perioperative PBI with multicather-interstitial brachytherapy were evaluated. While LC delineation using implanted catheters as fiducial markers was used as a reference, conventional LC was virtually delineated on computed tomography with clips. PTV1-cm margin and PTV2-cm margin, which means 1cm and 2cm expansion from LC, were developed and assumed for brachytherapy and externalbeam PBI, respectively. The target accuracy and the impact of the delineation accuracy of LC on PTVs were evaluated. The geographic miss index (GMI) and normal tissue index (NTI) were used as accuracy indices and were defined as the percentage of under- and overestimating volume, respectively.

The PTV1-cm margin and PTV2-cm margin were significantly larger than the reference volume, 57.9cm3 vs. 37.9cm3 (P<0.001) and 113.2cm3 vs. 93.8cm3 (P<0.001), respectively. The GMI and NTI of LC were 27.3% and 41.2%, respectively. Although the GMI in the PTV1-cm margin and PTV2-cm margin was significantly reduced to 9.8% (P<0.0001) and 9.9% (P<0.0001), respectively, the NTI was not significantly improved in the PTV1-cm margin, which was 41.8% (P=0.60) but was improved in PTV2-cm margin, which was 23.1% (P<0.0001).

The GMI in PTV1-cm margin was reduced to be as low as PTV2-cm margin. Although PTV2-cm margin was associated with lower NTI, the absolute volume was almost double with PTV1-cm margin. Although further research is required, brachytherapy-based PBI may be a reasonable option to achieve tumor control and cosmesis using the conventional delineation method.

Fibrocystic change (FCC) of the breast is one of the most common benign breast diseases commonly observed between 20-50 years, with a peak in the perimenopausal age group. Patients present with various symptoms such as lump in the breast, mastalgia (commonly related to the menstrual cycles) or nipple discharge.

In our retrospective study, which included 172 patients, the imaging findings were observed by ultrasound and X-ray mammogram. Based on the Breast Imaging Reporting and Data System (BI-RADS) guidelines given by the AmericanCollege ofRadiology (ACR), our imaging findings were classified as BI-RADS 2 in benign lesions, an d complicated cysts were classified as probably benign - BI-RADS 3. Indeterminate findings were classified as suspicious lesions and BI-RADS 4a/b/c. Imaging and histopathological correlation was performed.

Ultrasound findings revealed diffuse/bilateral abnormalities with the most common finding being simple cysts followed in descending order by complicated cysts, clustered cysts, complex solid cystic masses, solid lesions, duct ectasia, and intraductal lesions. Mammogram showed dense (type C or D) fibro glandular pattern obscuring the lesions, followed by well-defined/partly obscured opacities. Simple cysts and complicated cysts showed predominant features of cyst formation on HPE. Atypical hyperplasia was seen in ductal and complex solid cystic mass lesions.

It is essential for radiologists to be familiar with imaging and pathological findings of fibrocystic disease of the breast for further workup and management.

Mastalgia is common among women and its aetiology is still not fully understood. Many studies have been conducted to reveal the relationship between breast pain and psychosomatic disorders. The goals of the project are to compare the interaction of psychological symptoms and health related quality of life (HRQL) in patients with mastalgia between Eastern and Western Turkey.

Seventy-four women from the General Surgery Clinic of Diyarbakır Ergani Hospital (Eastern group) (n=39) and Istanbul University, Istanbul Faculty of Medicine (Western group) (n=35) were included in the study. The symptom checklist-90-revised (SCL-90-R) scale was used to evaluate physiological findings and Short Form-36 (SF-36) scale was used for evaluating health related quality of life (HRQL).

The median age of patients from Eastern group was 27.54 (18-39) years and 35.57 (18-70) years in Western group (t=-4.585, P<0.0001). Average Global Severity İndex (GSI) scores of the eastern group were statistically significantly higher than those of the western group (P<0.01). When the SCL-90-R values of the eastern and western groups were compared, somatization, interpersonal sensitivity, phobic anxiety, psychoticism, depression and anxiety in the eastern group were higher than in the western group. According to SF-36 results, the mean scores in the eastern group tended to be lower than those in the western group.

The results revealed that psychological symptoms differ between eastern and western Turkey. This may indicate that socio-economic differences may also have effects on psychological symptoms. In addition, mastalgia negatively affects women's quality of life.

Weight gain and excessive adiposity are associated with an increased risk of breast cancer, especially in postmenopausal women with a high circulating level of testosterone. In this in silico study, the effect of the dietary energy restriction (DER) on the expression of a panel of genes coding for the main enzymes involved in androgens and estrogens production was investigated in breast epithelium and abdominal adipose tissue of healthy women with excessive adiposity and randomly assigned to DER for one menstrual cycle or asked to continue their usual diet.

Wilcoxon-Signed-Rank test was used to assess the difference between paired samples before and after DER in the breast epithelium or adipose tissue, and Spearman’s rank correlation was used to investigate the correlation between genes.

In response to DER, the expression of HSD17B12, the gene encoding the enzyme that catalyzes the conversion of inactive estrone into bioactive estradiol, was significantly (P=0.0059) downregulated in breast epithelium and adipose tissue. Furthermore, the expression of HSD17B12 negatively correlated with that of the LRP1 gene (r=-0.91, P<0.0001), which codes for a multitasking protein recently proposed as a tumor suppressor in breast epithelium.

The results showed that, in addition to the recognized systemic effects (reduction of the fatty mass and decrease of circulating biomarkers of breast cancer risk), DER could act locally by down-regulating the expression of some genes pivotally involved in the production of biologically active estrogens, thus contributing to preventing the estrogen-dependent initiation of breast cancer.

Magnetic resonance imaging (MRI) is increasingly used in breast imaging. Diffusion imaging (DWI) is used in conjunction with contrast enhanced series. There is a signal difference between the stationary and moving water molecules in DWI, due to the fact that all molecules receive a first gradient pulse and then another pulse at the 180 degree-reverse direction of the first one. The stationary molecules have zero signal after the two of the pulses and show restriction (low signal). However, the moving molecule is not at the same location and escape from the 180 degree pulse with an energy in the end of the gradients. Multidirectional Diffusion-Weighted Imaging (MDDWI) gives information signifying water’s capacity to move freely in a direction according to its physiological and pathological boundaries, which is referred to as fractional anisotropy (FA). This study aimed to determine the usefulness of FA maps in differentiating benign and malignant breast lesions.

The patients who had breast MRI including MDDWI series and went through pathological evaluation (79 patients with 86 lesions) were included in the study. The FA values were measured in addition to the conventional Diffusion-ADC values. Also, diffusion restriction and pathology results were noted. The lesion FA and ADC values, diffusion assessment, and pathology results were compared using the Student t-test.

The patients were between 23 and 76 years and the mean age for benign lesions was 43.9, whereas it was 50.4 for the malignant lesions. Forty-five patients had benign and 41 had malignant lesions. The mean ADC values were significant between benign and malignant lesions (correspondingly; 1256.5x10–3 mm²/s. and 978.7x10–3 mm²/s.) The FASD value of each lesion was found to be significant for malignant lesions (100x10–3 ), especially those with restricted diffusion. In addition, for lesions with restricted diffusion, the maximum FA (75x10–3 ) and mean FA (200x10–3 ) values were found to be significant for malignancy. A cut-off point of 500×10–3 of FA max was found to be a value that could be used to increase the specificity of suspicious lesions with restricted diffusion

Restricted diffusion is used as a supporting finding for biopsy indication, but due to its lower specificity DWI cannot be very helpful in increasing the specificity of conventional breast MRI. In the search of finding a tool to increase the specificity of breast MRI, FA values seem to have the potential in differentiating benign lesions.

The experience of anxiety as a bad experience creates a different behavioral, cognitive, and emotional response that preserves annoying thoughts and inefficient beliefs. The present study aimed to investigate the effectiveness of acceptance and commitment therapy (ACT) and spirituality therapy in reducing anxiety in women with breast cancer in Tehran.

This was a pre-test/post-test quasi-experimental design research with a control group and a three-month follow-up. The statistical population comprised women with breast cancer visiting the Gynecological Ultra-Specialized Cancer Center of Khatam-al-Anbya Hospital in Tehran in 2021. In total, 45 women with breast cancer were selected and randomly divided into two experimental groups and one control group (n=15). The first and second experimental groups underwent eight 60-minute sessions of ACT and eight 60-minute sessions of spiritual therapy, respectively. The research instruments included the Penn State Worry Questionnaire (PSWQ). The collected data were analyzed using repeated measures ANOVA.

The results showed that ACT and spiritual therapy significantly reduced generalized anxiety scores in the experimental groups compared to the control group (P<0.01). Moreover, the absence of anxiety significantly increased in the two experimental groups that underwent ACT and spirituality therapy compared to the control group (P<0.01). However, ACT and spirituality therapy did not differ significantly in their effects on the dependent variables.

This study achieved promising results concerning the applicability of ACT and spirituality therapy in reducing anxiety in women with breast cancer. Based on the results, holding ACT and spirituality therapy workshops may exert beneficial effects on reducing anxiety in women with breast cancer

Diagnosis and treatment of breast cancer often involves several surgical procedures. Women with breast cancer are asked repeatedly to report their breast surgery history, often elicited in an open-ended format and relying on patient recall. Electronic medical records (EMR) and other medical documentation are not always readily available. No comprehensive, validated patient-reported measure of breast surgery history exists. We developed a close-coded, digital survey tool to elicit patient-reported breast surgery history (PRoBe-SH).

We administered the PRoBe-SH survey tool to a convenience sample of patients with a history of breast cancer. We compared PRoBe-SH data to both surgical history documented in patients’ EMR and open-ended surgical history ascertained from patient-completed clinic intake forms. Sensitivity/specificity analyses and McNemar’s tests were performed.

Data from fifty patients (median age 53.5 years, range 31-71, 70% nonHispanic white) were analyzed. The sensitivity of the PRoBe-SH for accurately identifying surgical history was 100% for mastectomy, lumpectomy 96%, mastectomy sidedness 100% (right) and 100% (left), lumpectomy sidedness 36% (right) 55% (left), lymphadenectomy 64%, breast reconstruction 89%, and presence of a native nipple 100% (right) and 100% (left). Open-ended surgical history was more than 90% sensitive for identifying mastectomy and lumpectomy only. The PRoBe-SH was significantly more sensitive than open-ended surgical history for identifying mastectomy sidedness (P<0.01), lymphadenectomy (P<0.01), and breast reconstruction (P<0.01).

Ascertaining accurate breast surgical history is important in the context of clinical care and for research purposes. The PRoBe-SH is a comprehensive, highly sensitive alternative to obtaining an open-ended breast surgical history when EMR data or other medical documentation are not available.

Screening mammography has limited sensitivity for detecting breast cancer in dense breast tissue. This study estimates the maximal number of breast cancers undetected by mammography in individuals with dense breast tissue participating in screening mammography in the United States.

Published data on supplemental screening incremental cancer detection rates (ICDRs), dense breast tissue prevalence, and total annual screening mammography exams in the United States are utilized for study estimates.

Assuming an ICDR of 16 cancers beyond mammography per 1,000 individuals with dense breast tissue, 38.8 million mammograms in the U.S. in 2021, and a prevalence of dense breast tissue of 43%, the number of cancers undetected by mammography in individuals with dense breast tissue participating in screening in the U.S. is estimated at 267,000.

A large number of undiagnosed breast cancers in the population of individuals with dense breast tissue participating in screening mammography is estimated.

Amyloidosis is characterised by extracellular accumulation of an amorphous fibrillary protein and can affect any organ. It is classified into systemic and localised disease according to its sites of presentation and as primary or secondary according to aetiology. Breast amyloid was first described in 1973 and is extremely rare.

A 61-year-old woman presented in 2020 with a 1-year history of an enlarging tender left nipple with some associated bleeding. Clinical differential diagnoses included a nipple adenoma and an intraductal carcinoma; therefore, a punch biopsy was taken. A full set of screening blood tests were undertaken which were normal, showing no evidence of a plasma cell dyscrasia. The biopsy showed diffuse replacement of the dermis by acellular eosinophilic material showing fracturing. Congo Red stain was positive showing apple-green birefringence under polarised light. A diagnosis of primary localised cutaneous nodular amyloidosis of the nipple was made.

We present a rare documented case of isolated primary localised cutaneous nodular amyloidosis of the nipple. This can be considered as a differential diagnosis for patients with a new nipple lesion alongside nipple adenoma and intraductal carcinoma.