scholarly journals Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments

2020 ◽  
Vol 8 (1) ◽  
pp. 18 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Hormone Receptors ◽  
Early Stage ◽  
Brca Mutation ◽  
Clonal Evolution ◽  
Metastatic Breast ◽  
Genetic Alterations ◽  
Telomere Maintenance ◽  
Molecular Features

Breast cancer is the most commonly occurring cancer in women. There were over two-million new cases in world in 2018. It is the second leading cause of death from cancer in western countries. At the molecular level, breast cancer is a heterogeneous disease, which is characterized by high genomic instability evidenced by somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The genomic instability is caused by defects in DNA damage repair, transcription, DNA replication, telomere maintenance and mitotic chromosome segregation. According to molecular features, breast cancers are subdivided in subtypes, according to activation of hormone receptors (estrogen receptor and progesterone receptor), of human epidermal growth factors receptor 2 (HER2), and or BRCA mutations. In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations and their clonal evolution during disease development. These studies have contributed to identify a repertoire of numerous disease-causing genes that are altered through different mutational processes. While early-stage breast cancer is a curable disease in about 70% of patients, advanced breast cancer is largely incurable. However, molecular studies have contributed to develop new therapeutic approaches targeting HER2, CDK4/6, PI3K, or involving poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and immunotherapy.

scholarly journals Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1331
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Olga Savichtcheva ◽  
Kimberly A. Holden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genomic Instability ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
T1 And T2 ◽  
Tumor Dna

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

scholarly journals Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer

2019 ◽  
Vol 30 (3) ◽  
pp. 412-417 ◽  
Author(s):  
E. Evron ◽  
A.M. Ben-David ◽  
H. Goldberg ◽  
G. Fried ◽  
B. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Brca Mutation ◽  
Contralateral Breast ◽  
Early Stage Breast Cancer ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
Prophylactic Irradiation

scholarly journals Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Duman BB ◽  
Cil T
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Hormone Receptor ◽  
Tumor Heterogeneity ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Her2 Overexpression

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

scholarly journals Biomarkers for HER2-positive metastatic breast cancer: Beyond hormone receptors

2020 ◽  
Vol 88 ◽  
pp. 102064 ◽  
Author(s):  
Maria Vittoria Dieci ◽  
Federica Miglietta ◽  
Gaia Griguolo ◽  
Valentina Guarneri
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptors ◽  
Metastatic Breast ◽  
Her2 Positive

Patient preferences for treatment of metastatic breast cancer: a study of women with early-stage breast cancer.

1995 ◽  
Vol 13 (4) ◽  
pp. 858-868 ◽  
Author(s):  
R P McQuellon ◽  
H B Muss ◽  
S L Hoffman ◽  
G Russell ◽  
B Craven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Life Expectancy ◽  
Metastatic Disease ◽  
Patient Preferences ◽  
Early Stage ◽  
Metastatic Breast ◽  
High Dose

PURPOSE The purpose of this study was to elicit preferences for the treatment of metastatic breast cancer in women with early-stage breast cancer who were given hypothetical treatment scenarios. We predicted that quality of life, demographic, and treatment variables would have an impact on patient preferences. PATIENTS AND METHODS One hundred fifteen patients with stage 1-IIIA breast cancer were interviewed. All patients had either mastectomy or lumpectomy plus radiotherapy as primary treatment. Sixty-seven (58%) had prior adjuvant chemotherapy. Patients were given four clinical scenarios that described a woman with metastatic breast cancer who was stated to have a life expectancy of 18 months. Side effects of the treatment options were systematically varied from low (hormonal therapy) to life-threatening (high-dose experimental therapy) and were consistent with common clinical situations. Patients were asked to select which treatment, with its associated toxicity, they would accept and prefer for a 50% chance of specified increments in life expectancy, ie, 5 years, 18 months, 1 year, 6 months, 1 month, and 1 week. RESULTS Quality of life at the time of interview, previous chemotherapy treatment, and degree of difficulty of previous treatments did not predict patient preferences. The greater the toxicity potential of the treatment, the less likely patients were to accept the treatment, although approximately 15% of patients would prefer high-risk treatment for as little as 1 month of added life expectancy. Between 34% and 82% of patients would prefer different therapies for a 6-month addition to life expectancy, whereas almost all patients would accept treatment for a 5-year increase in length of survival. Younger patients were more willing to assume the risks of treatment for a small increase in life expectancy. Of note, between 54% and 78% of patients would elect to start the different treatments even without symptoms related to metastatic disease. Moreover, 76% of patients would prefer standard treatment or an experimental agent to reduce symptoms or pain, even if such treatment did not prolong life. Additionally, only 10% of patients would allow randomization to a clinical trial comparing high-dose with standard chemotherapy. Participation in the study was not distressing to most patients. CONCLUSION Patients showed clear preferences for specific treatments for metastatic disease when given hypothetical scenarios. There was a wide range of patient preferences for treatment based on risk-benefit assessment, but a substantial percentage of patients would accept the risk of major toxicity for minimal increase in overall survival.

scholarly journals Evaluation of the HER2 and Hormone Receptor Status in Metastatic Breast Cancer Using Cell Blocks: A Multi-Institutional Study

2018 ◽  
Vol 62 (4) ◽  
pp. 288-294 ◽  
Author(s):  
Rieko Nishimura ◽  
Yuya Murata ◽  
Kiyoshi Mori ◽  
Katsushige Yamashiro ◽  
Kazuya Kuraoka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Routine Practice ◽  
Her2 Positive ◽  
Her2 Protein ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Epidermal Growth

Objective: We explore the problems associated with the cell block (CB) method for receptor analysis in breast cancer metastases and propose a method for reporting the results. Study Design: Nine institutions used the CB method for the analysis of hormone receptors (HRs) and HER2 (human epidermal growth factor receptor 2) protein in cytological specimens of breast cancer metastases in routine practice. The stained slides were independently evaluated by 8 pathologists. Dual in situ hybridization assay was performed in cases of discordant results for HER2 protein. Based on the results, we propose a method for receptor scoring in the CB method. Results: Of 61 specimens, 57 contained tumor cells. Two or more pathologists disagreed on the results for the estrogen receptor, progesterone receptor, and HER2 protein in 3 (5.3%), 13 (22.8%), and 19 (33.3%) cases, respectively. The discrepant results for the HRs were attributed to the presence of a few positive cells or faintly stained cells. The high interobserver discordance rate for HER2 protein was explained by interobserver differences in the scoring criteria. Conclusion: The use of categorical scoring into positive and negative is recommended for evaluating the HR expressions. Use of strict criteria for HER2 protein 2+ and 3+ cases is recommended, as HER2-positive cases should not be missed.

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