The natural history of HER2-overexpressing (HER2+) metastatic breast cancer (MBC) treated with trastuzumab (T): Practical points to consider in developing treatment strategies.

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Download Full-text

TMJ pain as a presentation of metastatic breast cancer to the right mandibular condyle

BMJ Case Reports ◽

10.1136/bcr-2021-241601 ◽

2021 ◽

Vol 14 (3) ◽

pp. e241601

Author(s):

Victor Ken On Chang ◽

Samuel Thambar

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Head And Neck ◽

Cancer Metastasis ◽

Mandibular Condyle ◽

Metastatic Breast ◽

Neck Region ◽

Head And Neck Region ◽

History Of ◽

The Right

Cancer metastasis to the oral and maxillofacial region is uncommon, and metastasis to the mandibular condyle is considered rare. We present a case of a 56-year-old woman with a history of invasive ductal cell carcinoma of the right breast, 10 years in remission, presenting with a 6-month history of symptoms typical of temporomandibular joint (TMJ) dysfunction. Imaging revealed an osteolytic lesion of her right TMJ and subsequent open biopsy confirmed the diagnosis of metastatic breast cancer. Despite the rarity of metastatic cancer to the head and neck region, it is still important for clinicians from both medical and dental backgrounds to consider this differential diagnosis, particularly in patients with a history of hormonal positive subtype of breast cancer. Given that bony metastasis can manifest even 10 years after initial diagnosis, surveillance which includes examination of the head and neck region is important, and may include routine plain-film imaging surveillance with an orthopantomogram (OPG).

Download Full-text

Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study

Breast Cancer Research ◽

10.1186/s13058-020-01349-9 ◽

2020 ◽

Vol 22 (1) ◽

Cited By ~ 1

Author(s):

Joyce O’Shaughnessy ◽

Christine Brezden-Masley ◽

Marina Cazzaniga ◽

Tapashi Dalvi ◽

Graham Walker ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Ovarian Cancer ◽

Risk Factor ◽

Metastatic Breast Cancer ◽

Family History ◽

Metastatic Breast ◽

Cytotoxic Chemotherapy ◽

First Line ◽

History Of

Abstract Background The global observational BREAKOUT study investigated germline BRCA mutation (gBRCAm) prevalence in a population of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Methods Eligible patients had initiated first-line cytotoxic chemotherapy for HER2-negative MBC within 90 days prior to enrollment. Hormone receptor (HR)-positive patients had experienced disease progression on or after prior endocrine therapy, or endocrine therapy was considered unsuitable. gBRCAm status was determined using baseline blood samples or prior germline test results. For patients with a negative gBRCAm test, archival tissue was tested for somatic BRCAm and homologous recombination repair mutations (HRRm). Details of first-line cytotoxic chemotherapy were also collected. Results Between March 2017 and April 2018, 384 patients from 14 countries were screened and consented to study enrollment; 341 patients were included in the full analysis set (median [range] age at enrollment: 56 [25–89] years; 256 (75.3%) postmenopausal). Overall, 33 patients (9.7%) had a gBRCAm (16 [4.7%] in gBRCA1 only, 12 [3.5%] in gBRCA2 only, and 5 [1.5%] in both gBRCA1 and gBRCA2). gBRCAm prevalence was similar in HR-positive and HR-negative patients. gBRCAm prevalence was 9.0% in European patients and 10.6% in Asian patients and was higher in patients aged ≤ 50 years at initial breast cancer (BC) diagnosis (12.9%) than patients aged > 50 years (5.4%). In patients with any risk factor for having a gBRCAm (family history of BC and/or ovarian cancer, aged ≤ 50 years at initial BC diagnosis, or triple-negative BC), prevalence was 10.4%, versus 5.8% in patients without these risk factors. HRRm prevalence was 14.1% (n = 9/64) in patients with germline BRCA wildtype. Conclusions Patient demographic and disease characteristics supported the association of a gBRCAm with younger age at initial BC diagnosis and family history of BC and/or ovarian cancer. gBRCAm prevalence in this cohort, not selected on the basis of risk factors for gBRCAm, was slightly higher than previous results suggested. gBRCAm prevalence among patients without a traditional risk factor for harboring a gBRCAm (5.8%) supports current guideline recommendations of routine gBRCAm testing in HER2-negative MBC, as these patients may benefit from poly(ADP-ribose) polymerase (PARP) inhibitor therapy. Trial registration NCT03078036.

Download Full-text

Treatment Strategies for Patients With Anthracycline- and Taxane-Pretreated Metastatic Breast Cancer

Seminars in Oncology ◽

10.1053/j.seminoncol.2008.02.009 ◽

2008 ◽

Vol 35 ◽

pp. A3-A4

Author(s):

Andrew D. Seidman

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Strategies ◽

Metastatic Breast

Download Full-text

Diabetic Ketoacidosis With Alpelisib

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.767 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A376-A377

Author(s):

Rebecca Jeun ◽

Victor Ralph Lavis ◽

Sonali Thosani

Keyword(s):

Breast Cancer ◽

Diabetes Mellitus ◽

Metastatic Breast Cancer ◽

Diabetic Ketoacidosis ◽

Hormone Receptor ◽

Previous History ◽

Metastatic Breast ◽

Laboratory Evaluation ◽

Hormone Receptor Positive ◽

History Of

Abstract Background: Hyperglycemia is a frequently reported adverse effect of alpelisib, an isoform specific phosphoinositide 3 kinase inhibitor, which is recently approved for use in hormone receptor positive advanced or metastatic breast cancer. Though two patients in clinical trials with alpelisib developed diabetic ketoacidosis (DKA), there have been no case reports to date characterizing this complication after drug approval. We present the first case of DKA in patients on alpelisib therapy. Clinical Case: A 55-year-old woman with a history of hormone-receptor positive metastatic breast cancer was started on treatment with fulvestrant and alpelisib. The patient did not have any previous history of diabetes nor gestational diabetes, though she had evidence of prediabetes prior to starting treatment. Patient was non-obese and had a family history of type 2 diabetes. Baseline hemoglobin A1c was 5.6% (n <5.7%) with impaired fasting glucose of 108 mg/dl (n<105 mg/dL) immediately prior to starting therapy. One week after starting alpelisib, she presented to the emergency center in diabetic ketoacidosis. Initial laboratory evaluation showed serum glucose 690 mg/dl, anion gap metabolic acidosis, with undetectable serum bicarbonate and ketonuria. C-peptide on hospital day 1 was found to be 2.8 ng/ml (n 0.5 - 3.4 ng/ml) with a concurrent glucose of 479 mg/dl. GAD65 and Islet Antigen 2 antibodies were negative. Diabetic ketoacidosis quickly resolved with continuous insulin infusion and stopping alpelisib. The patient was able to come off all insulin therapy prior to discharge and was discharged on metformin with adequate glycemic control. Conclusions: Current manufacturer guidelines for alpelisib recommend screening for diabetes mellitus at baseline and monitoring blood glucose and/or fasting plasma glucose weekly for the first two weeks of treatment and monthly thereafter. However, patients with no pre-existing history of diabetes mellitus may be at risk for life-threatening hyperglycemic crises which may develop within a week of initiation of alpelisib and more frequent monitoring may be indicated. The hyperglycemic effect of alpelisib appears to be reversible upon stopping the drug.

Download Full-text

Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes

Journal of Clinical Investigation ◽

10.1172/jci96149 ◽

2018 ◽

Vol 128 (4) ◽

pp. 1355-1370 ◽

Cited By ~ 47

Author(s):

Ikram Ullah ◽

Govindasamy-Muralidharan Karthik ◽

Amjad Alkodsi ◽

Una Kjällquist ◽

Gustav Stålhammar ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Lymph Nodes ◽

Evolutionary History ◽

Metastatic Breast ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

History Of

Download Full-text

Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer (MBC) patients in Sweden

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1088 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1088-1088

Author(s):

M. Lidgren ◽

C. Rehnberg ◽

N. Wilking ◽

B. Jönsson

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cost Effectiveness ◽

Treatment Strategies ◽

Metastatic Breast ◽

Chemotherapy Treatment ◽

Her2 Testing ◽

Trastuzumab Treatment ◽

Life Years ◽

The Cost

1088 Background: Trastuzumab is a monoclonal antibody that together with chemotherapy significantly improves time to progression and overall survival for MBC patients with tumours overexpressing HER2. The aim of this study was to analyse the cost- effectiveness of HER2 testing and trastuzumab in combination with chemotherapy compared with chemotherapy alone from a societal perspective in a Swedish setting. Methods: We used a Markov state transition model to simulate HER2 testing and subsequent treatment in a hypothetical cohort of 65 year old metastatic breast cancer patients based on the study by Marty et al (Marty et al, J Clin Oncol. Jul 1 2005;23(19):4265–4274). Outcomes included life-time costs, quality adjusted life years (QALY), and cost per QALY gained. Five different testing and treatment strategies were evaluated. Results: We estimated the cost per QALY gained to be about 485,000 SEK (approximately 70,000 USD) and the cost per life year (LY) gained to be about 332,000 SEK (approximately 47,000 USD) for the strategy of IHC testing for all patients, with FISH confirmation of 2+ and 3+, and trastuzumab and chemotherapy treatment for FISH positive patients. For the strategy of FISH testing for all patients, with trastuzumab and chemotherapy for FISH positive patients, we estimated the cost per QALY gained to about 561,000 SEK (approximately 80,000 USD) and the cost per LY gained to be 384,000 SEK (approximately 55,000 USD). The remaining testing and treatment strategies were dominated. Results were sensitive to changes in the quality adjustment of life years with metastatic disease, the risk of breast cancer related death, and test characteristics. Conclusions: Our analysis indicate that the present Swedish guidelines of IHC testing for all patients with metastatic breast cancer, with FISH confirmation of 2+ and 3+, followed by trastuzumab and chemotherapy treatment for FISH positive patients is a cost-effective treatment option. However, further research on budget impact of trastuzumab treatment and patient accessibility to trastuzumab treatment is needed. No significant financial relationships to disclose.

Download Full-text