A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM)

Purpose

To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology.

Methods

A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement.

Results

Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12–24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival.

Conclusions

High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.

     

Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive,human epidermal growth factor receptor 2-negative,metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG)

Purpose

To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2?), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community.

Methods

A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice.

Results

Level 1 evidence now supports use of a CDK 4/6 inhibitor in combination with endocrine therapy for patients with HR+, HER2?, mBC. Currently, there are no biomarkers that reliably define patients who will, or will not, benefit from the addition of a CDK 4/6 inhibitor to their endocrine therapy. Additional research is needed to identify the optimal sequencing of CDK 4/6 inhibitors in relation to other therapies as well as the optimal duration of therapy; at present, evidence suggests that use in the upfront setting is better than waiting for a later line of therapy, or adding after endocrine therapy has started.

Conclusions

Thus far, three CDK 4/6 inhibitors—palbociclib, ribociclib, and more recently, abemaciclib—have been approved for use in the setting of HR+, HER2?, mBC.  The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation.

     

Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year,monocentric, retrospective study

Background

Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum–taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS).

Methods

We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007–2016 with the combination of carboplatin AUC 2 plus paclitaxel 80 mg/m², both given on days 1 and 8 in every 21-day cycle.

Results

264 patients were evaluable for treatment safety and activity. The objective response rate (ORR) was 44.7%. Median PFS and OS were 8.6 and 23.7 months, respectively. Triple-negative breast cancer (TNBC) patients had significantly lower PFS and OS times compared to other biology groups. At multivariable analysis, previous exposure to taxanes, HR-positive HER2-negative biology, a higher number of metastatic sites, and de novo metastatic disease at diagnosis were associated with reduced PFS, while receiving maintenance therapy correlated with improved PFS. Overall, the treatment was quite well tolerated, with 10.2% of patients discontinuing one or both drugs because of adverse events (AEs). G3–G4 neutropenia occurred in 16.8% of patients, while the incidence of febrile neutropenia was 2.3%.

Conclusions

Weekly carboplatin–paclitaxel regimen is active and well tolerated in mBC treatment. Prospective studies should be conducted to compare its efficacy and tolerability with standard single-agent paclitaxel or docetaxel treatment schedules, as well as with more recent combination regimens.

     

Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer: a single-center prospective observational study

Purpose

Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the clinicopathologic factors that predict the outcome of routine trastuzumab therapy remain unclear.

Methods

The outcome and safety profile of trastuzumab therapy in untreated HER2 positive AGC was evaluated in this prospective observational study. Clinical and pathological data including demographics, treatment profiles, expression level of HER2 were analyzed to identify predictive factors of trastuzumab-based first-line therapy for their progression-free survival (PFS).

Results

Overall, 107 patients were eligible. The median number of treatment cycles was 9 (range 1–44), the median PFS and median overall survival (OS) were 7.7 months (95% CI 6.5–8.9) and 16.0 months (95% CI 13.2–18.8), respectively. The confirmed response rate was 58.9%, and the disease control rate was 82.2%. Patients with liver metastasis (HR 1.616) and poor performance status (PS, HR 2.518) were independently associated with a worse PFS, while the other clinicopathological factors including demographics, treatment profiles and some other clinical characteristics did not predict the survival.

Conclusions

In routine clinical practice, the addition of trastuzumab to chemotherapy was effective and safe in real-world setting in Chinese patients with HER2 positive AGC, regardless of most of the clinicopathological factors. Further studies are needed to improve the prognosis of HER2 positive patients with liver metastasis or poor PS. Trial Registration clinicaltrials.gov Identifier: NCT03024450

     

African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages

Purpose

Racial disparity of breast cancer in each subtype and substage is not clear.

Methods

We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.

Results

African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.

Conclusion

AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

     

HER4 expression in estrogen receptor-positive breast cancer is associated with decreased sensitivity to tamoxifen treatment and reduced overall survival of postmenopausal women

Background

The sensitivity of estrogen receptor-positive breast cancers to tamoxifen treatment varies considerably, and the molecular mechanisms affecting the response rates are manifold. The human epidermal growth factor receptor-related receptor HER2 is known to trigger intracellular signaling cascades that modulate the activity of coregulators of the estrogen receptor which, in turn, reduces the cell sensitivity to tamoxifen treatment. However, the impact of HER2-related receptor tyrosine kinases HER1, HER3, and, in particular, HER4 on endocrine treatment is largely unknown.

Methods

Here, we retrospectively evaluated the importance of HER4 expression on the outcome of tamoxifen- and aromatase inhibitor-treated estrogen receptor-positive breast cancer patients (n =?258). In addition, we experimentally analyzed the efficiency of tamoxifen treatment as a function of HER4 co-expression in vitro.

Results

We found a significantly improved survival in tamoxifen-treated postmenopausal breast cancer patients in the absence of HER4 compared with those with pronounced HER4 expression. In accordance with this finding, the sensitivity to tamoxifen treatment of estrogen and HER4 receptor-positive ZR-75-1 breast cancer cells can be significantly enhanced by HER4 knockdown.

Conclusion

We suggest an HER4/estrogen receptor interaction that impedes tamoxifen binding to the estrogen receptor and reduces treatment efficiency. Whether the sensitivity to tamoxifen treatment can be enhanced by anti-HER4 targeting needs to be prospectively evaluated.

     

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis

Aim

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy.

Methods

This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013.

Results

The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS.

Conclusion

Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

     

HER2 Activating Mutations in Estrogen Receptor Positive Breast Cancer

Purpose of Review

HER2 activating mutations are a new, druggable mutation identified by next-generation DNA sequencing (NGS) of breast cancer. Here, we review the recent data on the diagnosis and treatment of HER2 mutated, metastatic breast cancer.

Recent Findings

Pre-clinical studies have shown that HER2 activating mutations accelerate tumor growth and can be inhibited by HER2 targeted drugs, including trastuzumab and the second-generation, pan-HER tyrosine kinase inhibitor, neratinib. HER2 mutations can be diagnosed by NGS testing on either a tumor biopsy or circulating tumor DNA obtained from peripheral blood. Case reports provided initial evidence that HER2 targeted therapies can effectively treat patients with HER2 mutated, metastatic breast cancer. Two phase II clinical trials, MutHER and SUMMIT, both demonstrate that neratinib monotherapy has clinical efficacy for these patients, with clinical benefit rate of 31–40%.

Summary

HER2 targeted therapies are effective for HER2 mutated breast cancer but emergence of drug resistance remains a problem. Clinical trials are now testing neratinib-containing drug combination regimens for HER2 mutated, metastatic breast cancer patients.

     

Clinical and pathological characterization of HER2 mutations in human breast cancer: a systematic review of the literature

Purpose

HER2 gene is a member of the epidermal growth factor receptor (EGFR) family. Across different malignancies, aberrations of HER2 gene commonly correspond to gain-of-function alterations leading to increased receptor signaling.

Methods

We have reviewed the literature currently available on HER2 mutations in human breast cancer (BC) evaluating type and frequency of such mutations. The primary objective was to determine the frequency and the number of patients with HER2-mut in the series analyzed. The secondary objectives were to assess characteristics of mutated cases (ER and HER2 status and stage of disease, type of mutations, and finally the clinical outcome if reported).

Results

We retrieved 31 published papers, and the pooled rate of HER2 mutations across 12,905 BC patients was calculated. Overall, the frequency of HER2 mutations was 2.7% with most involving the intracellular domain. About 4% of patients were finally mutated. The predictive role was not described. Only 30% of these patients were simultaneously HER2 positive and 63% were ER positive.

Conclusion

We have found that the prevalence of HER2 mutations is about 3%. These genic alterations are independently associated with HER2 amplification status, occurring in both ER-positive/HER2-negative diseases or HER2-enriched cancers. Ongoing trials are investigating small molecules tyrosine kinase inhibitors in patients harboring these mutations.

     

Optimizing HER2-Directed Therapy in Early-Stage Breast Cancer

Purpose of Review

HER2-positive early breast cancer has been revolutionized by the development of HER2-directed therapy, which has significantly reduced breast cancer recurrence risk and improved overall survival. Here, we review the available treatment options for this patient population and discuss how we might individualize therapy in the future to optimize the balance of efficacy and toxicity.

Recent Findings

The addition of pertuzumab to a trastuzumab-based adjuvant regimen improves pathologic complete response rates and invasive disease-free survival (DFS). Addition of neratinib for patients with high-risk disease also contributes to improved DFS.

Summary

Current data supports use of dual HER2-directed therapy in combination with chemotherapy, as well as extended HER2-directed therapy (beyond 1 year), in those with high-risk HER2-positive early breast cancer. Ongoing studies aim to identify biomarkers of response and resistance to standard approaches, as well as identify those who might benefit from a chemotherapy-free treatment paradigm.

     

Effect of everolimus treatment for regrown renal angiomyolipoma associated with tuberous sclerosis complex after transcatheter arterial embolization

Background

The aim of this study was to evaluate the effects and the utility of second-line everolimus treatment for regrown renal angiomyolipoma (AML) with tuberous sclerosis complex (TSC) after transcatheter arterial embolization (TAE).

Methods

We investigated a total of 14 patients who underwent second-line everolimus treatment for TSC–AML that regrew after TAE, and assessed their effects and adverse events. Everolimus treatment was performed for AML with a maximum diameter of 4 cm. To determine the reduction ratio of AML, the volume of AML was measured using multislice helical computed tomography. Adverse events were evaluated according to CTCAE v4.0-JCOG. We further compared the treatment effect and adverse events with those in patients receiving first-line everolimus treatment.

Results

The AML volume decreased in all patients, with a?≥?50% volume decrease in 57% (8 of 14) of the cases, and the mean reduction rate was 53%. We observed no significant difference in the mean reduction rate of AML between second-line everolimus treatment for regrown TSC–AML after TAE and first-line everolimus treatment for TSC–AML. The adverse events were mild and consistent with those reported in our previous study.

Conclusion

Although further studies are needed, everolimus appears to be effective as second-line treatment for TSC–AML that regrew after TAE and a beneficial treatment option for TSC–AML.

     

Fortgeschrittenes Magenkarzinom

Background

Systemic chemotherapy has become established as the standard treatment for advanced incurable gastric cancer. In the metastatic setting, systemic chemotherapy can prolong the survival time, improve symptom control and help to maintain a better quality of life.

Material and methods

Testing the human epidermal growth factor receptor 2 (HER2) expression status of the primary tumor and/or metastases is warranted before initiation of first-line treatment.

Results

In cases of HER2 overexpression or amplified tumors, trastuzumab in combination with cisplatin and 5?fluorouracil (5-FU) or capecitabine are the standard forms of treatment. Tumors that are HER2 negative or weakly positive are treated with a platinum-fluoropyrimidine combination as doublet or as a triplet with docetaxel in younger patients who can tolerate more intensive treatment. Taxane derivatives, such as docetaxel and paclitaxel as well as irinotecan are accepted treatment options for patients who show progress during or after first-line chemotherapy. The anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) antibody ramucirumab demonstrated efficacy with prolongation of survival both as monotherapy and in combination with paclitaxel.

Objective

This review article outlines the indications and clinical data for pharmaceutical treatment of advanced gastric cancer.

     

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer

Background

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC.

Methods

This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression.

Results

The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001–1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2.

Conclusion

Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

     

Afatinib,an Irreversible EGFR Family Inhibitor,Shows Activity Toward Pancreatic Cancer Cells,Alone and in Combination with Radiotherapy,Independent of <Emphasis Type="Italic">KRAS</Emphasis> Status

Background

Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients.

Objective

Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells.

Methods

The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis.

Results

Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS ^wt) and Capan-2 (KRAS ^mut) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio-induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS ^mut) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization.

Limitations

These results must be confirmed in vivo.

Conclusions

Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status.

     

The yield of full <Emphasis Type="Italic">BRCA1</Emphasis>/<Emphasis Type="Italic">2</Emphasis> genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations

Purpose

Patients treated with trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) are living longer, but there is little information on their outcomes and treatment experience beyond the median survival from clinical trials and real-world observational studies. We aim to describe the real-world treatment patterns and overall survival (OS) for women surviving five or more years from initiation of trastuzumab for HER2+MBC.

Methods

This is a retrospective, whole-of-population cohort study of women initiating trastuzumab for HER2+MBC between 2001 and 2011, followed to 2016. We defined long-term survivors (LTS) as those patients surviving?≥?5 years from trastuzumab initiation. We used dispensing claims to describe timing of cancer treatments used by LTS and to estimate time on and off HER2-targeted therapies, and OS from trastuzumab initiation for HER2+MBC.

Results

Of 4177 women initiating trastuzumab for HER2+MBC, 1082 (26%) survived ≥?5 years. Median age for LTS was 54 years (IQR 46–63). At a median follow-up of 9.4 years, 36% of LTS died; their conditional probability of surviving an additional 5 years was 55%. Median time on trastuzumab and all HER2-targeted therapy was 58.9 months (27.6–88.1) and 69.1 months (35.6–124.5), respectively. 85% of LTS had a period off HER2 therapy, lasting a median of 30.4 months (8.2–NR).

Conclusions

LTS generally receive HER2-targeted therapies for periods of time longer than in clinical trials, but most LTS also had breaks in treatment. More research is needed to understand the effects of long-term treatment and to identify patients who may be able to safely discontinue HER2-targeted therapy.

     

Immunotherapy in Breast Cancer: the New Frontier

Purpose of review

This review summarizes current immunotherapies in breast cancer, with an emphasis on immune checkpoint inhibitors and vaccines.

Recent findings

Combination immunotherapy with checkpoint inhibitors and cytotoxic therapies have shown promising results. Active clinical trials are ongoing in both early stage and metastatic settings for triple negative, HER2+, and hormone-positive breast cancer patients.

Summary

Ongoing challenges remain in defining biomarkers that predict response to immunotherapy, determining the optimal combination immunotherapies, and enhancing the immunogenicity of breast cancer subtypes.

     

Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC-06)

Background

S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC.

Methods

Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1–28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle.

Results

A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65–85). The confirmed response rate was 40.8% (95% CI 27.1–54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death.

Conclusions

Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC.

Clinical trials registration

UMIN000007368.

     

Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?

Purpose

To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.

Methods

Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m² every 21 days for unfit patients or (2) docetaxel 75 mg/m² every 21 days for fit patients.

Results

Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.

Conclusions

This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

     

Incidence,Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

Purpose of Review

Treatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here, we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment.

Recent Findings

Screening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy. Because trastuzumab-induced cardiotoxicity is typically reversible, cessation of trastuzumab and/or administration of first-line heart failure agents effectively restores cardiac function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough that the risk-benefit ratio still weighs in favor of its use in the vast majority of patients with HER2+ breast cancer.

Summary

An improved understanding of the pathophysiology underlying trastuzumab-induced cardiotoxicity and the identification of patients at highest risk will allow us to continue to safely administer trastuzumab in patients with breast cancer.

     

Novel Targets in Advanced Colorectal Cancer

Purpose of Review

Although current guidelines suggest only testing for RAS and BRAF mutations as well as MMR deficiency in metastatic colon cancer, there are many other promising therapeutic targets that are being studied. We aim to review the recent literature and evidence behind some of these novel targets.

Recent Findings

Many of these targets such as NTRK, ROS, ALK, and HER2 are being studied in current clinical trials and hold great potential in changing the treatment landscape for metastatic colorectal cancer.

Summary

Current molecular testing algorithms may need to be expanded to allow better target discovery and for patients to benefit from more therapeutic options.