Use of LH-RH agonists in the treatment of breast disease

1989 ◽  
Vol 95 ◽  
pp. 271-281
Author(s):  
R. I. Nicholson ◽  
K. J. Walker
Keyword(s):  
Breast Cancer ◽  
Premenopausal Women ◽  
Breast Disease ◽  
Breast Cancer Patients ◽  
Surgical Ablation ◽  
Current Application ◽  
Er Positive ◽  
Premenopausal Patients ◽  
Combined Endocrine Therapy ◽  
Lh Rh

SynopsisThe effects of LH-RH agonists in advanced breast cancer patients are reviewed and compared to the efficacy of surgical ablation of the ovaries and X-ray induced menopause in the treatment of this disease. In both pre- and postmenopausal women, LH-RH agonists produce pituitary gland desensitisation and a fall in concentrations of LH and FSH. In premenopausal patients plasma progesterone and oestradiol levels fall to the castrate or postmenopausal range within three to four weeks. Tumour remissions have been observed in approximately 30% of premenopausal women (50% ER-positive) and approximately 10% of postmenopausal patients. The mechanism of action of LH-RH agonists is discussed and their current application to combined endocrine therapy, early breast cancer and mastalgia briefly outlined.

Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

1996 ◽  
Vol 14 (1) ◽  
pp. 46-51 ◽  
Author(s):  
S E Rivkin ◽  
S Green ◽  
J O'Sullivan ◽  
A B Cruz ◽  
M D Abeloff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Operable Breast Cancer ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Er Positive ◽  
Premenopausal Patients ◽  
Positive Breast Cancer

PURPOSE To determine whether the addition of surgical ovariectomy to standard chemotherapy prolongs disease-free survival (DFS) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes. PATIENTS AND METHODS Three hundred fourteen premenopausal patients with ER-positive, node-positive breast cancer were enrolled between July 1979 and July 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive either of the following: (1) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (i.v.) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 i.v. weekly for 1 year, vincristine .625 mg/m2 i.v. weekly for the first 10 weeks, and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (2) bilateral ovariectomy followed by CMFVP. RESULTS The median follow-up time is 7.7 years and the maximum 13.2 years. Treatment arms are not significantly different with respect to either survival or DFS (one-sided log-rank, P = .55 and .70, respectively). The 7-year survival rate is 71% on the CMFVP arm and 73% on CMFVP plus ovariectomy. No significant differences were observed in node or receptor level subsets. CONCLUSION We conclude that, in this study, the addition of ovariectomy did not improve results over chemotherapy alone in the treatment of premenopausal women with node-positive, ER-positive, operable breast cancer. Our sample size was too small to detect a small improvement. The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22 (95% confidence interval [CI], .79 to 1.89).

scholarly journals Expression of Insulin Receptor and c-MET Is Associated with Clinicopathologic Characteristics and Molecular Subtypes in Premenopausal Breast Cancer Patients

2020 ◽  
Vol 10 (5) ◽  
pp. 1614
Author(s):  
Nehad M. Ayoub ◽  
Rami J. Yaghan ◽  
Alia H. Al-Mohtaseb ◽  
Najla Aldaoud ◽  
Ismail I. Matalka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Insulin Receptor ◽  
Cancer Patients ◽  
Molecular Subtypes ◽  
Menopausal Status ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Premenopausal Breast Cancer ◽  
Er Positive ◽  
Premenopausal Patients

Receptor Tyrosine Kinases (RTKs) represent a class of transmembrane receptors known to play an important role in cancer development and progression. In this study, the expression of insulin receptor (IR) and the hepatocyte growth factor receptor (c-MET) was examined in breast cancer patients. Immunohistochemistry for IR and c-MET was performed on 71 cases of invasive breast cancer and expression scores were correlated with clinicopathologic characteristics and molecular subtypes and further stratified based on a menopausal status. Expression of IR was significantly associated with the tumor grade (p = 0.017) and estrogen receptor (ER) expression (p = 0.015). There was a significant positive correlation between IR and c-MET expression scores (rho = 0.458, p < 0.001). Among premenopausal cases, IR scores were significantly higher in patients with grade I/II disease (p = 0.025), ER-positive (p = 0.030), and progesterone receptor (PR)-positive carcinoma (p = 0.015). c-MET expression scores were significantly higher among premenopausal patients with ER-positive (p = 0.007) and PR-positive carcinoma (p = 0.024). IR expression scores were significantly different among molecular subtypes for all patients (p = 0.006) and among premenopausal cases (p = 0.035). c-MET expression was statistically different among molecular subtypes for premenopausal patients (p = 0.019). Survival analysis revealed that the expression status of IR and c-MET was not associated with overall survival. Our findings support a favorable prognostic value for IR and c-MET expression in premenopausal breast cancer patients.

Attitude towards Aggression and Creative Functioning in Patients with Breast Cancer

1998 ◽  
Vol 87 (1) ◽  
pp. 291-303 ◽  
Author(s):  
Åsa Lilja ◽  
Gudmund Smith ◽  
Per Malmström ◽  
Leif G. Salford
Keyword(s):  
Breast Cancer ◽  
Healthy Subjects ◽  
Premenopausal Women ◽  
Breast Cancer Patients ◽  
Personality Tests ◽  
Identification Test ◽  
Contrast Technique ◽  
Discriminant Analyses ◽  
Premenopausal Patients ◽  
Surprising Finding

Three projective personality tests were used to assess attitude to aggression (The Identification Test), anxiety and defenses (The Meta-Contrast Technique) and creative functioning (The Creative Functioning Test) in 70 patients with breast cancer. Discriminant analyses were applied pro primo to characterize psychologically patients with a better prognosis and patients with a poorer prognosis. A second aim was to characterize psychologically older (postmenopausal) and younger (premenopausal) women. Generally, high scores on the Identification Test indicated maladaptive attitudes towards aggression among all the patients. Patients with a poorer prognosis showed responses that in healthy subjects indicate acknowledgement of aggressive impulses, perhaps suggesting lack of “defenses” against such impulses among those patients. Another way to describe it would be that patients with a better prognosis seem to have (normally nonadaptive) “defenses” against aggressive impulses while those with poorer prognosis have not. Surprisingly, the patients with a better prognosis (but not those with a poorer prognosis) gave responses classified as depression in the Meta-Contrast Technique. Typical of premenopausal patients were responses classified as anxiety as well as reaction formation on the Identification Test. Responses classified as adaptive defenses (isolation) were seen in the Meta-Contrast Technique. A surprising finding was that many of these patients were characterized by high scores on the creativity test. These original statistically significant findings of attitudes towards aggression and creative functioning in breast cancer patients are discussed in relation to the underlying nature of aggression and creativity.

In Vivo Measurements of Fibrin Formation and Fibrinolysis in Operable Breast Cancer

1989 ◽  
Vol 61 (02) ◽  
pp. 318-321 ◽  
Author(s):  
P McCulloch ◽  
J Douglas ◽  
G D O Lowe ◽  
G Murray ◽  
W D George
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Degradation Products ◽  
Breast Disease ◽  
Breast Diseases ◽  
Breast Cancer Patients ◽  
Fibrin Formation ◽  
Er Positive ◽  
Malignant Breast

SummaryFibrin formation and fibrinolysis were estimated in 89 breast cancer patients by measurement in plasma of Fibrin Fragment Bβ 15-42 and Fibrinopeptide A (FPA), serum Fibrin(ogen) Degradation Products (FDPs) and plasminogen activator by Fibrin Plate Lysis Assay. Results were compared with (a) 26 patients with benign breast diseases; and (b) 45 healthy factory workers. FPA, FDP and Bβ 15-42 Levels were elevated in both breast cancer patients and benign disease patients, but there were no significant differences between these two groups. Cancer stage, patient age and smoking habits did not affect these results, but Oestrogen Receptor (ER) positive patients had higher Bβ 15-42 values than ER negative patients (p = 0.017). These results show that fibrin formation is enhanced preoperatively in patients with either benign or malignant breast disease. The fibrinolytic response to activated coagulation may be relatively deficient in breast cancer. The roles of malignancy, stress and other factors in the causation of these abnormalities require further assessment.

Tamoxifen in premenopausal patients with metastatic breast cancer: a review.

1991 ◽  
Vol 9 (7) ◽  
pp. 1283-1297 ◽  
Author(s):  
M C Sunderland ◽  
C K Osborne
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Menopausal Status ◽  
Metastatic Breast ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Er Positive ◽  
Premenopausal Patients

The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy in Premenopausal Patients With Node-Positive Breast Cancer: The Zoladex Early Breast Cancer Research Association Study

2002 ◽  
Vol 20 (24) ◽  
pp. 4628-4635 ◽  
Author(s):  
W. Jonat ◽  
M. Kaufmann ◽  
W. Sauerbrei ◽  
R. Blamey ◽  
J. Cuzick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Side Effects ◽  
Association Study ◽  
Early Breast Cancer ◽  
Research Association ◽  
Node Positive ◽  
Er Positive ◽  
Premenopausal Patients ◽  
Positive Breast Cancer

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

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