Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening.
Smith Robert A,Andrews Kimberly,Brooks Durado,DeSantis Carol E,Fedewa Stacey A,Lortet-Tieulent Joannie,Manassaram-Baptiste Deana,Brawley Otis W,Wender Richard C
CA: a cancer journal for clinicians
Each year the American Cancer Society (ACS) publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, we summarize current ACS cancer screening guidelines, including the update of the breast cancer screening guideline, discuss quality issues in colorectal cancer screening and new developments in lung cancer screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey.
Adherence to lifestyle-related cancer prevention guidelines and breast cancer incidence and mortality.
Cifu Gabriella,Arem Hannah
Annals of epidemiology
PURPOSE:Breast cancer is the most common cancer in women. Many lifestyle factors have been associated with an increased risk of breast cancer incidence and mortality. An index-based approach to analyzing adherence to American Cancer Society (ACS) guidelines as a whole may better explain associations between lifestyle variables and breast cancer incidence and mortality. METHODS:We created an index based on American Cancer Society-specific guidelines, including body mass index (BMI), physical activity, alcohol intake, tobacco use, daily time spent watching television, and certain dietary habits. Cox proportional hazards regression was used to model the association between the lifestyle index and primary breast cancer and breast cancer-specific mortality in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) cohort. RESULTS:We identified 7088 women with incident breast cancer, 1162 deaths overall, and 462 deaths due to breast cancer. Compared with the lowest quintile of lifestyle index score (meeting fewest guidelines), women in the highest quintile had a 24% lower risk of breast cancer (hazard ratio [HR] = 0.76, 95% CI: 0.70, 0.82) and 37% lower risk of all-cause mortality (HR = 0.63, 95% CI: 0.53, 0.76), while the association with breast cancer-specific mortality was nonsignificant. CONCLUSIONS:Healthier prediagnosis lifestyle is associated with a decreased risk of breast cancer and all-cause mortality in the NIH-AARP cohort.
Comparison of 4th ESO-ESMO international consensus guidelines for advance breast cancer and Chinese anti-cancer association committee of Breast Cancer Society guideline.
Hu Xichun,Li Ting,Wang Biyun,Zhang Jian,Yu Xiaoli,Shao Zhimin
Breast (Edinburgh, Scotland)
The primary aim of the international advance breast cancer (ABC) guidelines are to guide treatment decisions in many different healthcare settings, but need adaptations due to different access to care. These guidelines are based on the most up-to-date evidence. However, Chinese experts have a different national condition and policies to face. The Chinese Anti-Cancer Association Committee of Breast Cancer Society guideline (CBCS guideline) is to guide treatments and to reflect unmet needs of Chinese breast cancer patients. Although, most of the recommendations in the two guidelines are the same, some of them are different. In this article, with regard to country-specific peculiarities, a working group of Chinese breast cancer experts compare the similarities and differences between the ABC guideline and CBCS guideline and commented on the voting results of the ABC panelists. We also discuss why these differences exist, such as lack of access, different tumor biology and epidemiology, and even different culture. The money which patients have to pay out of pocket for their medical cost and the availability of drugs lie at the heart of the issues of guideline differences.
NCCN Guidelines Updates: Breast Cancer.
Giordano Sharon H,Elias Anthony D,Gradishar William J
Journal of the National Comprehensive Cancer Network : JNCCN
The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor-positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy. Most of the benefit is modest and toxicity is an issue; therefore, extended-duration endocrine therapy should be highly individualized. For triple-negative disease, platinum agents and PARP inhibitors are helping some patients, but immunotherapies and other novel classes of drugs now in development hold the promise of even better outcomes. In HER2-positive early-stage disease, dual HER2 blockade is of modest benefit, and extended treatment with neratinib may be a good option for some high-risk patients.
ASCO 2018 highlights: metastatic breast cancer.
Rinnerthaler Gabriel,Gampenrieder Simon Peter,Greil Richard
This article reviews the clinically most relevant presentations at the American Society of Clinical Oncology (ASCO) annual meeting 2018 on the topic of metastatic breast cancer. In the randomized placebo-controlled phase 3 trial MONALEESA-3, testing ribociclib vs. placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative (HER2-) advanced breast cancer (ABC), an increase of median progression-free survival (PFS) from 12.8 months to 20.5 months by the addition of the CDK4/6 inhibitor was reported (HR 0.59; > 0.01). Taselisib, an alpha specific PI3K inhibitor, was tested in combination with fulvestrant in pretreated HR+/HER2- ABC patients with PIK3CA mutations in the placebo-controlled phase 3 trial SANDPIPER. PFS was significantly longer (7.4 months vs 5.4 months; HR 0.70, < 0.01) but severe adverse events were more frequent (32% and 9%) in the taselisib group. In triple-negative breast cancer, the AKT inhibitor capivasertib (AZD5363) was combined with paclitaxel as first-line treatment in the placebo-controlled phase 2 trial PAKT. In patients with altered PIK3CA, AKT1 or PTEN, median PFS increased from 3.7 months to 9.3 months (HR 0.30; two-sided = 0.01). No treatment effect was shown in the non-altered group. The most common adverse events attributed to capivasertib were diarrhea, fatigue and stomatitis. Results of two phase I trials of trastuzumab antibody-drug conjugates (ADCs) indicated HER2 as a non-oncogenic surface target in breast cancer patients expressing HER2.
A systematic review of the international prevalence of mutation in breast cancer.
Armstrong Nigel,Ryder Steve,Forbes Carol,Ross Janine,Quek Ruben Gw
A systematic review was conducted, summarizing international or () mutation prevalence in breast cancer. Databases (eg, Medline and Embase; N=7) and conferences were searched (January 2012 to December 2017). From 17,872 records, 70 studies were included. In 58 large (N>100) studies, mutation prevalence varied widely from 1.8% (Spain) in sporadic breast cancer to 36.9% (United States) in estrogen receptor/progesterone receptor low+ (1-9% on immunohistochemistry/human epidermal growth factor receptor 2-negative [HER2-]) breast cancer. In 2 large studies unselected for family history, ethnicity, sex, or age and no/unclear selection by breast cancer stage or hormone receptor (HR) status, germline (g) mutation prevalence was 2.9% (Italy) to 3.0% (South Korea). In the 4 large unselected triple-negative breast cancer studies, g mutation prevalence varied from 9.3% (Australia) to 15.4% (United States). g mutation prevalence in 1 large unselected HR positive/HER2- early breast cancer study was 5% (United States). In 2 large unselected metastatic breast cancer studies, g mutation prevalence was 2.7% (France) and 4.3% (Germany). Locally advanced breast cancer studies were small and not in unselected populations. Poor reporting of g status and basis of selection implies a need for further large well-reported mutation prevalence studies in breast cancer.
SABCS 2017: lifestyle factors, hormone receptor-positive advanced disease, liquid biopsies, and prognosis.
Rinnerthaler Gabriel,Gampenrieder Simon Peter,Greil Richard
This article reviews the clinically most relevant presentations at the San Antonio Breast Cancer Symposium (SABCS) 2017 on the topics lifestyle factors, hormone receptor-positive advanced disease, liquid biopsies, and prognosis. In a retrospective analysis of the Women's Health Initiative Observational Study, a reduction in the body mass index (BMI) of at least 5% within 3 years significantly reduced the risk of breast cancer compared to women with a stable weight (HR 0.77; 95% CI 0.78-0.98). In the MONALEESA-7 trial investigating ribociclib or placebo in combination with endocrine therapy as first-line treatment in pre- and perimenopausal women with hormone receptor-positive, human epidermal growth factor 2 (HER2)-negative metastatic breast cancer, a significantly longer progression-free survival was shown for patients treated with ribociclib compared to the placebo group (23.8 vs. 13.0 months; HR 0.55; 95% CI 0.43-0.72; < 0.001). In a pooled toxicity and efficacy analysis of elderly women treated with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in combination with an aromatase inhibitor in first-line, toxicities of higher grade were more common in elderly compared to younger patients, despite comparable efficacy. And the Clinical Treatment Score post-5 years (CTS5), accurately estimated the risk of late recurrence after 5 years of adjuvant endocrine treatment using routinely available clinical parameters.
Management of hormone-receptor positive human epidermal receptor 2 negative advanced or metastatic breast cancers.
Ngan Roger K C
Annals of translational medicine
Hormone therapy, rather than chemotherapy, is recommended for hormone-receptor positive (HR+), human epidermal receptor 2 negative (HER2-) advanced or metastatic breast cancer (A/MBC) according to the European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines, unless in visceral crisis in which chemotherapy is indicated. Hormonal monotherapy of selective estrogen receptor modulator (SERM) or selective estrogen receptor down-regulator (SERD), aromatase inhibitor (AI), or their combination as doublets, used to be the mainstay options as first-line (1L) therapy for most patients. More recently, combination targeted drugs plus AI or SERD (such as fulvestrant) has been extensively investigated in both 1L and second-line (2L) treatments of HR+ HER2- patients. Cyclin-D kinase 4/6 inhibitors (CDK4/6i) can halt tumor proliferation by blocking the ER related transcription signaling that drives the CDK4/6-dependent cell cycle in HR+ tumors, and they work best together with AI or SERD. On the other hand, favorable results were reported from inhibition of m-TOR pathway, both in 2L setting when PI3K-AKT-mTOR pathway is frequently overexpressed, as well as in 1L setting. Currently, the major guidelines have all included CDK4/6i plus AI as a standard 1L therapy, while Everolimus plus AI, and CDK4/6i plus fulvestrant, are recommended 2L options. Selecting appropriate patients for such therapeutic options and harnessing the sequence of these new therapies in the new paradigm of managing HR+ HER2- A/MBC are the key priorities for future clinical research.
Combination Therapies in Advanced, Hormone Receptor-Positive Breast Cancer.
Journal of the advanced practitioner in oncology
About 17% of women with breast cancer have locally advanced or metastatic disease at the time of diagnosis, and 30% to 40% of women diagnosed with early-stage disease will eventually have recurrence. The majority of breast cancers express estrogen or progesterone receptors, and hormonal therapies (HTs) remain the treatment of choice for these cancers after the resection of primary tumors. In addition to their effectiveness, HTs often have fewer severe side effects compared with chemotherapies. As breast cancer recurs or progresses, however, it becomes less responsive to successive HT, and the duration of response decreases. Recent advances have identified specific combinations of HTs that can extend the duration of response in appropriate patients with advanced breast cancer. Furthermore, research into signaling pathways has led to the availability of targeted agents that improve efficacy and duration of response when used in combination with specific HTs. Despite their effectiveness and advantages, these combination therapies increase the burden of side effects and the care required for proper management. In addition, practitioners must educate patients about the increasing complexity regarding treatment decisions, and provide care as part of a patient-centered team that optimizes both the medical outcomes and quality of life of patients with breast cancer.
Association of Cytokines and Chemokines in Pathogenesis of Breast Cancer.
King Jeronay,Mir Hina,Singh Shailesh
Progress in molecular biology and translational science
Breast cancer touches women's life worldwide. Expected outcome is not achieved due to molecular heterogeneity and complex biology despite substantial advancement in diagnosis, prevention and treatment of breast cancer. Patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) positive tumors receive hormone ablation and Her2 directed therapy. While patients diagnosed with triple-negative breast cancer receive chemotherapy in both the early and advanced stages. However, chemotherapeutic efficacies are not the same in every patient, which has fostered a major effort to identify new targets to treat breast cancer. Positive therapeutic outcome after immune checkpoint inhibitors emphasizes the significance of the host immune system in breast cancer. Cancer develops in immune competent host wherein cytokines, while shaping the immune system, also serve as growth signals for cancer cells. The dynamics of cross talk between immune system and cancer cells mediated by cytokines and chemokines changes during cancer initiation, progression, and therapeutic interventions. Hence, better understanding of molecular footprint of cancer cells, as well as crosstalk between cancer cells and host immune system is needed to develop patient specific treatment and management of breast cancer.
Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies.
Lambertini Matteo,Santoro Luigi,Del Mastro Lucia,Nguyen Bastien,Livraghi Luca,Ugolini Donatella,Peccatori Fedro A,Azim Hatem A
Cancer treatment reviews
BACKGROUND:Breast cancer is composed of distinct subtypes defined mainly based on the expression of hormone receptors (HR) and HER2. For years, reproductive factors were shown to impact breast cancer risk but it is unclear whether this differs according to tumor subtype. In this meta-analysis we evaluated the association between parity, age at first birth, breastfeeding and the risk of developing breast cancer according to tumor subtype. METHODS:PubMed and Embase were searched to identify epidemiological studies that evaluated the impact of parity and/or age at first birth and/or breastfeeding on breast cancer risk with available information on HR and HER2. Tumor subtypes were defined as: luminal (HR-positive, HER2-negative or HER2-positive), HER2 (HR-negative, HER2-positive) and triple-negative (HR-negative, HER2-negative). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. The MOOSE guidelines were applied. RESULTS:This meta-analysis evaluated 15 studies, including 21,941 breast cancer patients and 864,177 controls. Parity was associated with a 25% reduced risk of developing luminal subtype (pOR 0.75; 95% CI, 0.70-0.81; p<0.0001). Advanced age at first birth was associated with an increased risk of developing luminal subtype (pOR 1.15; 95% CI, 1.00-1.32; p=0.05). Ever breastfeeding was associated with a reduced risk of developing both luminal (pOR 0.77; 95% CI, 0.66-0.88; p=0.003) and triple-negative (pOR 0.79, 95% CI, 0.66-0.94; p=0.01) subtypes. CONCLUSIONS:The reproductive behaviors impact the risk of developing breast cancer but this varies according to subtype.
Harbeck Nadia,Penault-Llorca Frédérique,Cortes Javier,Gnant Michael,Houssami Nehmat,Poortmans Philip,Ruddy Kathryn,Tsang Janice,Cardoso Fatima
Nature reviews. Disease primers
Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.
Advances in chemical pharmacotherapy to manage advanced breast cancer.
Gombos Andrea,Awada Ahmad
Expert opinion on pharmacotherapy
INTRODUCTION:Advanced breast cancer is still incurable. However, patients diagnosed with this fatal disease live longer. The selection of systemic therapy is mainly based on molecular subtype. The aim of management in these patients is to not only improve outcome, but also to maintain quality of life. Areas covered: In this paper we focus on available treatments and drugs under late development in the three main subtypes of breast cancer: luminal (hormone receptor positive), HER2 positive and triple negative disease. Main advances during the last years have been made in the treatment of HER2 positive breast cancer with the approval of several new targeted agents. Luminal breast cancer is also a field of active clinical research. So far triple negative breast cancer remains the subtype with the worse prognosis, even though new discoveries have been made to better understand the huge heterogeneity of this type of breast cancer. Expert opinion: Several new treatment options have recently been established in metastatic breast cancer. Side effects are sometimes cumbersome for the patient and are difficult to manage easily. Thus, identification of patients who derive the most benefit is needed. In addition, collaborative efforts should integrate the genotypic fragmentation in the management and future clinical research strategies of metastatic breast cancer patients.
Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer.
Sammons Sarah,Kornblum Noah S,Blackwell Kimberly L
Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy. As most patients in this setting have already developed mechanisms of resistance to endocrine therapy, targeting biological pathways associated with endocrine resistance in combination with fulvestrant may improve outcomes. Therefore, evidence supporting a combinatorial treatment approach in the second-line setting was investigated based on a search of PubMed and ClinicalTrials.gov . Twenty-eight studies of targeted therapies plus fulvestrant as second-line treatment for HR+ ABC were identified, including three and six key randomized trials exploring cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors plus fulvestrant respectively. Additional combinations with fulvestrant included inhibitors of epidermal growth factor receptors, androgen receptor, and the bromodomain and extra-terminal family of proteins. Across the studies reviewed with available data, the addition of targeted therapies to fulvestrant resulted in clinically meaningful improvements in progression-free survival compared with fulvestrant alone. While some challenging toxicities were observed, most adverse events could be effectively managed. Selection of second-line targeted therapy for use with fulvestrant should consider prior treatment as well as the mutation status of the tumor. In conclusion, available data indicate that fulvestrant combined with agents targeting mechanisms of endocrine resistance is a promising approach. The ongoing trials identified in this review will help further inform the selection of combination treatments with fulvestrant for HR+ ABC.
Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.
Clinical breast cancer
For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia.
Clinical Implications of the Progression-Free Survival Endpoint for Treatment of Hormone Receptor-Positive Advanced Breast Cancer.
Kaklamani Virginia G
UNLABELLED:: Hormonal therapy for advanced breast cancer (ABC) has evolved significantly since the introduction of tamoxifen more than 40 years ago. The availability of selective antiestrogen therapies has further improved treatment options for women with hormone receptor-positive (HR+) ABC. However, with the development of resistance to hormonal therapies, a new treatment paradigm has emerged based on our understanding of biological pathways involved in HR+ breast cancer and mechanisms of resistance to hormonal therapy. Recent drug development efforts have focused on combining hormonal treatment with agents that target mammalian target of rapamycin serine-threonine kinases and cyclin-dependent kinases. In parallel with the evolution of hormonal and targeted therapies, our understanding of the utility of clinical endpoints has deepened. Progression-free survival (PFS) is a primary endpoint well-understood by clinicians and is increasingly accepted as a surrogate for overall survival (OS) by the U.S. Food and Drug Administration. Yet the perceived clinical benefit of PFS to patients is less well understood. Patients may not grasp the implications of prolonged PFS, highlighting the reality that patient preference in treatment selection encompasses factors that extend beyond drug activity. This presents an opportunity for clinicians to discuss PFS with patients in the context of their treatment plans, clinical outcomes, and quality-of-life measures. The objective of this review is to explore the clinical validity of the PFS and OS endpoints and the clinical relevance of PFS and OS to patients, especially in light of drivers that led to a range of treatment options for patients with HR+ ABC. IMPLICATIONS FOR PRACTICE:Advances in drug development during the past two decades have provided numerous options for treatment of advanced breast cancer that include monotherapy with endocrine modulating agents and dual therapy that combines endocrine therapy with an inhibitor targeting the mammalian target of rapamycin serine-threonine kinase or cyclin-dependent kinase pathways known to be involved with resistance. Clinical trial endpoints for breast cancer have evolved as well. Communication of progression-free survival, overall survival, and other outcomes with patients should incorporate the context of the individual's treatment plan and include discussion of response rate, side effects, and quality of life.
Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order.
Perez Edith A
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Although survival rates among patients with breast cancer have improved in recent years, those diagnosed with advanced disease with distant metastasis face a 5-year survival rate of less than 25%, making the management of these patients an area still in significant need of continued research. Selecting the optimal treatment order from among the variety of currently available therapy options presents a relevant challenge for medical oncologists. With the understanding that the majority of patients with breast cancer and those who succumb to this disease have HR-positive disease, this review will focus on treatment options and treatment order in patients with HR-positive advanced breast cancer. While endocrine therapy is considered the preferred treatment for first-line therapy in HR-positive/HER2-negative breast cancer, selection of the specific agent depends on the menopausal status of the patient. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is also recommended as first-line treatment in patients with ER-positive/HER2-negative disease. In patients with endocrine therapy-resistant disease, specific strategies include sequencing of other antiestrogen receptor agents, or agents that target other molecular pathways. Future treatment strategies for patients with primary or secondary resistance to endocrine therapy for advanced disease are discussed. These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene.
Hormone receptor positive breast cancer: state of the art.
Peddi Parvin F
Current opinion in obstetrics & gynecology
PURPOSE OF REVIEW:Hormone receptor (HR) positive breast cancer represents the vast majority of breast cancer cases. Treatment for these patients has been 5 years of endocrine therapy in the localized setting and endocrine therapy alone in the metastatic setting until progression of disease and switch to chemotherapy until quite recently. RECENT FINDINGS:The current article will review recent data on role of extended endocrine therapy with tamoxifen and aromatase inhibitors and adjuvant bisphosphonates in the localized disease setting. It will then review the role of targeted agents such as cyclin dependent kinases 4/6 inhibitors, two of which were FDA approved in 2017 in the metastatic setting and are now standard of care. SUMMARY:Landscape of HR positive breast cancer is changing with doubling of progression-free survival with drugs approved in the last 2 years. Although antiestrogen therapy remains the backbone of therapy, we are continuing to improve outcome for patients by changes and additions to this therapy.
Hormone receptor-positive, HER2-negative metastatic breast cancer: redrawing the lines.
Matutino A,Joy A A,Brezden-Masley C,Chia S,Verma S
Current oncology (Toronto, Ont.)
Estrogen receptor modulators and estrogen deprivation have become standards of care for hormone receptor-positive metastatic breast cancer. However, after traditional first-line endocrine monotherapy treatment, the disease typically progresses despite the initial high rate of clinical benefit. Multiple studies have aimed at optimizing treatment strategies to improve upon clinical benefit beyond the traditional single-agent endocrine treatment. With the availability of new data and novel therapies, the clinical practice challenge becomes how best to define the optimal treatment sequence to maximize clinical benefit. In this review, we present treatment options clinically relevant to the management of hormone-positive, her2-negative metastatic breast cancer, and we propose a treatment algorithm based on the current literature.
From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?
Wu Victoria Shang,Kanaya Noriko,Lo Chiao,Mortimer Joanne,Chen Shiuan
The Journal of steroid biochemistry and molecular biology
Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease.
Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer.
Kolarova Iveta,Vanasek Jaroslav,Odrazka Karel,Melichar Bohuslav,Ryska Ales,Petera Jiri,Vosmik Milan,Dolezel Martin
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
Breast cancer with high expression of human epidermal growth factor receptor (HER)-2 represents a biologically and clinically heterogeneous group of neoplastic disorders. Importantly, hormone receptor expression has an effect on biological properties and affects the selection of therapies. On the basis of molecular genetics, four principal subtypes, including luminal A, luminal B, HER2-enriched (HER-2-E), and basal-like can be distinguished. Breast tumors characterized by HER-2 positivity and simultaneous expression of hormone receptors, triple positive breast cancers (TPBC) are of increasing interest owing to the unique biological characteristics associated with complex interactions between HER-2 and hormone receptor signaling pathways. Interactions between hormone receptors and HER-2 explain the decreased efficacy of hormonal therapy in comparison with HER-2-negative patients. The expression of estrogen receptors in HER-2 positive tumors may also be associated with resistance to anti-HER-2 treatment. Multiple available therapeutic options, including hormonal therapy, anti-HER-2 agents and cytotoxic drugs explain favorable prognosis of TPBC. Escalation and de-escalation therapeutic strategies that could result in lower toxicities are being investigated as well as combinations of anti-HER-2 agents with hormonal therapy, immunotherapy, cyclin dependent kinase 4/6 and phosphatidyl inositol-3-kinase inhibitors. Distinction between subtypes of HER-2-positive breast cancer and treatment diversification may result in improved outcomes in TPBC. A response to neoadjuvant therapy may serve in the tailoring of therapy management.
Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis.
Poggio F,Ceppi M,Lambertini M,Bruzzi P,Ugolini D,Bighin C,Levaggi A,Giraudi S,D'Alonzo A,Vaglica M,Blondeaux E,Sertoli M R,Pronzato P,Del Mastro L
Breast (Edinburgh, Scotland)
BACKGROUND:Although in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS). METHODS:Relevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016. The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method). RESULTS:A total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643). No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529). CONCLUSION:Our pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.