Does intraductal breast cancer spread in a segmental distribution? An analysis of residual tumour burden following segmental mastectomy using tumour bed biopsies

2001 ◽  
Vol 27 (1) ◽  
pp. 21-25 ◽  
Author(s):  
A.D. Jenkinson ◽  
R.A.M. Al-Mufti ◽  
Y. Mohsen ◽  
M.J. Berry ◽  
C. Wells ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Residual Tumour ◽  
Tumour Burden ◽  
Cancer Spread ◽  
Segmental Mastectomy

A distinct role in breast cancer for two LIV-1 family zinc transporters

2008 ◽  
Vol 36 (6) ◽  
pp. 1247-1251 ◽  
Author(s):  
Kathryn M. Taylor
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Prognostic Indicator ◽  
Breast Cancer Metastasis ◽  
Zinc Transporters ◽  
Aberrant Expression ◽  
Disease States ◽  
Cancer Spread ◽  
Protein Transporters

Zinc, essential for normal cell growth, is tightly controlled in cells by two families of zinc transporters. The aberrant expression of zinc transporters from the LIV-1 family of ZIP (Zrt/Irt-like protein) transporters is increasingly being implicated in a variety of disease states. In the present paper, I describe a mechanism for the role of ZIP7 in the progression of breast cancer, identifying it as a new target in breast cancer. Furthermore, I document a link between another zinc transporter, LIV-1, and breast cancer metastasis, identifying it as a potential new prognostic indicator of breast cancer spread.

scholarly journals Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer

2007 ◽  
Vol 96 (10) ◽  
pp. 1526-1531 ◽  
Author(s):  
W C M Duivenvoorden ◽  
S Vukmirović-Popović ◽  
M Kalina ◽  
E Seidlitz ◽  
G Singh
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Human Breast Cancer ◽  
Tumour Burden ◽  
Human Breast ◽  
Metastasis Model

scholarly journals Alteration in Steroid Hormone and HER2/neu Receptor Status Following Neoadjuvant Chemotherapy in Triple Negative Breast Cancer. Is There Any Hope?

2021 ◽  
Author(s):  
Rama Das ◽  
Parna Basu ◽  
Suman Ghosh ◽  
Debasish Guha
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Control Group ◽  
Study Group ◽  
Residual Tumour ◽  
Receptor Status ◽  
Platinum Based Chemotherapy

Introduction: Breast cancer continues to be the most common cancers among women in India. The Triple Negative Breast Cancer (TNBC) is a heterogeneous group of malignancy which is often aggressive and has a worse prognosis. Aim: The aim of this study was to assess the hormone receptor and HER2/neu status with platinum based chemotherapy in TNBC. Materials and Methods: The study was analysed retrospectively in a tertiary care centre of West Bengal from Januay 2017 to December 2019. Forty TNBC patients of Locally Advanced Breast Cancer (LABC) cases who received carboplatin along with neoadjuvant chemotherapy (study group) were compared with other group of 64 TNBC patients (control group) who did not receive any chemotherapy making a total of 104 cases of TNBC patients who were selected for the study. All the patients in both the groups had modified radical mastectomy. The study group of 40 TNBC patients who received chemotherapy also showed pathological partial response. Masterchart was prepared comprising patient’s age, menopausal status, family history, therapy history, histo-morphological features, hormone receptor and HER2/neu status after platinum added chemotherapy. Oestrogen Receptor (ER)/Progesterone Receptor (PR) were considered positive, if >1% tumour cell nuclei were immunoreactive and negative, if it was otherwise. HER-2/neu score of 3+ was taken as positive by Immunohistochemistry (IHC) method. Statistical analysis for descriptive purposes, percentages and mean were calculated. Comparison of both the groups was done by Pearson’s Chi-squared and Fisher’s-exact test. Significance level was considered at p-value <0.05. Results: TNBC patients (NACT group) showed hormone receptor positivity of 21 cases (52.50%) after chemotherapy along with carboplatin. HER2/neu positivity was detected in 9 (22.5%) cases. Non-NACT (64) cases were considered as control group for comparison. The effect of NACT in TNBC patients was found to be statistically significant with respect to change in HER2/neu (p=0.033, p<0.05) and ER status (p<0.05) while change in PR status was found to be statistically insignificant. Conclusion: The study showed significant alteration in hormonal and HER2/neu receptor status in TNBC patients receiving platinum added neoadjuvant chemotherapy. This study found statistical significance and justifies re-evaluation of these Hormone Receptor (HR) and HER2/neu markers in residual tumour after chemotherapy.

Metastatic breast cancer spread to peripancreatic lymph nodes causing biliary obstruction

2020 ◽  
Vol 26 (3) ◽  
pp. 511-513
Author(s):  
Naomal Perera ◽  
Nishani Fernando ◽  
Ranali Perera ◽  
Prasanna Jayasekara ◽  
Bimalka Senevirathne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Biliary Obstruction ◽  
Metastatic Breast ◽  
Cancer Spread

Management of Breast Cancer During Pregnancy Using a Standardized Protocol

1999 ◽  
Vol 17 (3) ◽  
pp. 855-855 ◽  
Author(s):  
David L. Berry ◽  
Richard L. Theriault ◽  
Frankie A. Holmes ◽  
Valerie M. Parisi ◽  
Daniel J. Booser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Combination Chemotherapy ◽  
Radical Mastectomy ◽  
First Trimester ◽  
Therapeutic Interventions ◽  
Outpatient Chemotherapy ◽  
Gestational Age At Delivery ◽  
Segmental Mastectomy ◽  
First Trimester Of Pregnancy

PURPOSE: No standardized therapeutic interventions have been reported for patients diagnosed with breast cancer during pregnancy. Of the potential interventions, none have been prospectively evaluated for treatment efficacy in the mother or safety for the fetus. We present our experience with the use of combination chemotherapy for breast cancer during pregnancy. PATIENTS AND METHODS: During the past 8 years, 24 pregnant patients with primary or recurrent cancer of the breast were managed by outpatient chemotherapy, surgery, or surgery plus radiation therapy, as clinically indicated. The chemotherapy included fluorouracil (1,000 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2), administered every 3 to 4 weeks after the first trimester of pregnancy. Care was provided by medical oncologists, breast surgeons, and perinatal obstetricians. RESULTS: Modified radical mastectomy was performed in 18 of the 22 patients, and two patients were treated with segmental mastectomy with postpartum radiation therapy. This group included patients in all trimesters of pregnancy. The patients received a median of four cycles of combination chemotherapy during pregnancy. No antepartum complications temporally attributable to systemic therapy were noted. The mean gestational age at delivery was 38 weeks. Apgar scores, birthweights, and immediate postpartum health were reported to be normal for all of the children. CONCLUSION: Breast cancer can be treated with chemotherapy during the second and third trimesters of pregnancy with minimal complications of labor and delivery.

scholarly journals Association between Lymph Node Status and Expression Levels of Androgen Receptor, miR-185, miR-205, and miR-21 in Breast Cancer Subtypes

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tatiana S. Kalinina ◽  
Vladislav V. Kononchuk ◽  
Alisa K. Yakovleva ◽  
Efim Y. Alekseenok ◽  
Sergey V. Sidorov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Expression Profiles ◽  
Lymph Node Status ◽  
Her2 Positive ◽  
Expression Levels ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Cancer Spread

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.

High Levels of Cathepsin B Predict Poor Outcome in Patients with Breast Cancer

1998 ◽  
Vol 13 (3) ◽  
pp. 139-144 ◽  
Author(s):  
T.M. Maguire ◽  
S.G Shering ◽  
C.M. Duggan ◽  
E.W. McDermott ◽  
N.J. O'Higgins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Plasminogen Activator ◽  
Tumor Size ◽  
Cathepsin B ◽  
Nodal Status ◽  
Chi Square ◽  
Poor Outcome ◽  
Cancer Spread ◽  
Er Status

Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and metastasis. Other proteases involved in cancer spread such as urokinase-type plasminogen activator (uPA) and cathepsin D have previously been shown to be prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with primary breast cancer. CB levels were significantly higher in both primary and metastatic breast tumors than in fibroadenomas (p=0.0001). In the primary carcinomas, CB levels showed no significant correlation with either nodal status, tumor size or estrogen receptor (ER) status. Patients with primary breast cancers containing high levels of CB had a significantly shorter disease-free interval (p=0.01, chi-square=6.61) and overall survival (p=0.014, chi-square=6.08) than patients with low levels of the protease. However, in multivariate analysis, using nodal status, tumor size, ER status and urokinase plasminogen activator (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER status and uPA were prognostic in multivariate analysis. In conclusion, CB, like certain other proteases implicated in cancer metastasis, correlates with poor outcome in patients with breast cancer. These results thus support the evidence from model systems linking CB to cancer spread. Inhibition of CB expression or activity might therefore be exploited for anti-metastatic therapies.

The PARP inhibitor, olaparib, depletes the ovarian reserve in mice: implications for fertility preservation

2020 ◽  
Vol 35 (8) ◽  
pp. 1864-1874 ◽  
Author(s):  
Amy L Winship ◽  
Meaghan Griffiths ◽  
Carolina Lliberos Requesens ◽  
Urooza Sarma ◽  
Kelly-Anne Phillips ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Parp Inhibitor ◽  
Brca2 Mutation ◽  
Primordial Follicle ◽  
Parp Inhibitors ◽  
Tumour Burden ◽  
Brca1 And Brca2 ◽  
Primordial Follicles ◽  
Intraperitoneal Dose ◽  
The Impact

Abstract STUDY QUESTION What is the impact of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, alone or in combination with chemotherapy on the ovary in mice? SUMMARY ANSWER Olaparib treatment, when administered alone, depletes primordial follicle oocytes, but olaparib does not exacerbate chemotherapy-mediated ovarian follicle loss in mice. WHAT IS KNOWN ALREADY The ovary contains a finite number of oocytes stored within primordial follicles, which give rise to all mature ovulatory oocytes. Unfortunately, they are highly sensitive to exogenous DNA damaging insults, such as cytotoxic cancer treatments. Members of the PARP family of enzymes are central to the repair of single-strand DNA breaks. PARP inhibitors have shown promising clinical efficacy in reducing tumour burden, by blocking DNA repair capacity. Olaparib is a PARP1/2 inhibitor recently FDA-approved for treatment of BRCA1 and BRCA2 mutation carriers with metastatic breast cancer. It is currently being investigated as an adjunct to standard treatment at an earlier stage, potentially curable, BRCA1- and BRCA2-associated breast cancer which affects reproductive age women. Despite this, there is no preclinical or clinical information regarding the potential impacts of olaparib on the ovary or on female fertility. Unfortunately, it may be many years before clinical data on fertility outcomes for women treated with PARP inhibitors becomes available, highlighting the importance of rigorous preclinical research using animal models to establish the potential for new cancer therapies to affect the ovary in humans. We aimed to comprehensively determine the impact of olaparib alone, or following chemotherapy, on the ovary in mice. STUDY DESIGN, SIZE, DURATION On Day 0, mice (n = 5/treatment group) were administered a single intraperitoneal dose of cyclophosphamide (75 mg/kg/body weight), doxorubicin (10 mg/kg), carboplatin (80 mg/kg), paclitaxel (7.5 mg/kg) or vehicle control. From Days 1 to 28, mice were administered subcutaneous olaparib (50 mg/kg) or vehicle control. This regimen is proven to reduce tumour burden in preclinical mouse studies and is also physiologically relevant for women. PARTICIPANTS/MATERIALS, SETTING, METHODS Adult female wild-type C57BL6/J mice at peak fertility (8 weeks) were administered a single intraperitoneal dose of chemotherapy, or vehicle, then either subcutaneous olaparib or vehicle for 28 days. Vaginal smears were performed on each animal for 14 consecutive days from Days 15 to 28 to monitor oestrous cycling. At 24 h after final treatment, ovaries were harvested for follicle enumeration and immunohistochemical analysis of primordial follicle remnants (FOXL2 expressing granulosa cells), DNA damage (γH2AX) and analysis of apoptosis by TUNEL assay. Serum was collected to measure circulating anti-Müllerian hormone (AMH) concentrations by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE Olaparib significantly depleted primordial follicles by 36% compared to the control (P &lt; 0.05) but had no impact on other follicle classes, serum AMH, corpora lutea number (indicative of ovulation) or oestrous cycling. Primordial follicle remnants were rarely detected in control ovaries but were significantly elevated in ovaries from mice treated with olaparib alone (P &lt; 0.05). Similarly, DNA damage denoted by γH2AX foci was completely undetectable in primordial follicles of control animals but was observed in ∼10% of surviving primordial follicle oocytes in mice treated with olaparib alone. These observations suggest that functional PARPs are essential for primordial follicle oocyte maintenance and survival. Olaparib did not exacerbate chemotherapy-mediated follicle depletion in the wild-type mouse ovary. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION This study was performed in mice, so the findings may not translate to women and further studies utilizing human ovarian tissue and sera samples should be performed in the future. Only one long-term time point was analysed, therefore olaparib-mediated follicle damage should be assessed at more immediate time points in the future to support our mechanistic findings. WIDER IMPLICATIONS OF THE FINDINGS Olaparib dramatically depleted primordial follicles and this could be attributed to loss of intrinsic PARP-mediated DNA repair mechanisms. Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility. Notably, the extent of follicle depletion might be enhanced in BRCA1 and BRCA2 mutation carriers, and this is the subject of current investigations. Together, our data suggest that fertility preservation options should be considered for young women prior to olaparib treatment, and that human studies of this issue should be prioritized. STUDY FUNDING/COMPETING INTEREST(S) This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the National Health and Medical Research Council (NHMRC); (K.J.H. #1050130) (A.L.W. #1120300). K.A.P. is a National Breast Cancer Foundation Fellow (Australia—PRAC-17-004). K.A.P. is the Breast Cancer Trials (Australia) Study Chair for the OlympiA clinical trial sponsored by AstraZeneca, the manufacturer of olaparib. All other authors declare no competing financial or other interests.

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