Breast cancer is the most frequent cause of cancer of women in much of the world. In countries with screening programs, breast cancer is often detected before clinical symptoms are apparent, but occasionally the occurrence of a paraneoplastic syndrome precedes the identification of cancer. In breast cancer, there are known to be paraneoplastic endocrine syndromes and neurologic syndromes. The neurologic syndromes are often hard to identify and treat. The neurologic syndromes associated with breast cancer include cerebellar degeneration, sensorimotor neuropathy, retinopathy, stiff-persons syndrome, encephalitis, and opsoclonus–myoclonus. Most of these are mediated by antibodies against known neural antigens, although some cases appear to be mediated by non-humoral mechanisms. Treatments differ depending upon the syndrome type and etiology. Outcomes also vary depending upon duration of disease, the treatments used and the responsiveness of the underlying cancer. A thorough review of the published literature is provided along with recommendations for management and future research.

BackgroundBreast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial.MethodsA vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, −A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid. The vaccine was administered on days 1, 8, 15, 36, 57, 78. CD8+ T cell responses to the vaccine were assessed by both direct and stimulated interferon gamma ELIspot assays.ResultsTwelve patients with breast cancer were treated: five had estrogen receptor positive disease and five were HER2 amplified. There were no dose-limiting toxicities. Toxicities were limited to Grade 1 and Grade 2 and included mild injection site reactions and flu-like symptoms, which occurred in most patients. The most common toxicities were injection site reaction/induration and fatigue, which were experienced by 100% and 92% of participants, respectively. In the stimulated ELIspot assays, peptide-specific CD8+ T cell responses were detected in 4 of 11 evaluable patients. Two patients had borderline immune responses to the vaccine. The two peptides derived from CEA were immunogenic. No difference in immune response was evident between patients receiving endocrine therapy and those not receiving endocrine therapy during the vaccine series.ConclusionsPeptide vaccine administered in the adjuvant breast cancer setting was safe and feasible. The TLR3 adjuvant, poly-ICLC, plus helper peptide mixture provided modest immune stimulation. Further optimization is required for this multi-peptide vaccine/adjuvant combination.Trial registration ClinicalTrials.gov (posted 2/15/2012): NCT01532960. Registered 2/8/2012. https://clinicaltrials.gov/show/NCT01532960 Electronic supplementary materialThe online version of this article (10.1186/s40425-017-0295-5) contains supplementary material, which is available to authorized users.

Cancer therapies, especially anthracyclines and monoclonal antibodies, have been linked with increased rates of cardiotoxicity. The development of some cardiac side effects happens over several months, and changes in ejection fraction can be detected long before permanent damage or disability occurs. Advanced heart failure could be averted with better and earlier detection. Methodologies for early detection of cardiac changes include stress echocardiograms, cardiac velocity measurements, radionuclide imaging, cardiac MRI and several potential biomarkers. Many agents have been described for prophylaxis of cardiac events precipitated by cancer therapy. Prophylactic use of beta-blockers and ACE inhibitors may be considered for use with trastuzumab in breast cancer as tolerated. Recovery of cardiac function is possible early after the injury from a cancer therapy. Late complications for coronary artery disease, hypertension and arrhythmia are underappreciated. Treatments for severe cancer therapy-related cardiac complications follow the existing paradigms for congestive heart failure and coronary artery disease, although outcomes for cancer patients differ from outcomes for non-cancer patients.

Some chemotherapeutic agents cause cardiotoxic effects including reduction in left ventricular ejection fraction (LVEF) and occasionally congestive heart failure. Anthracyclines and HER2 monoclonal antibodies are common offenders, but clinical practice data on LVEF changes, risk factors and acute recovery is lacking. We retrospectively examined the electronic medical record at an academic medical center for receipt of anthracyclines and/or trastuzumab from 2000 to 2013 in cancer patients. Patient characteristics and serial LVEF assessments were collected. Patients with and without LVEF decline were analyzed by univariate and multivariate analysis. A total of 549 patients were identified with anthracycline/trastuzumab use and 216 had multiple LVEF assessments. Only 27 of the 216 patients who had multiple LVEF assessments at multiple occasions suffered a clinically significant LVEF fall (12.5 %), and symptomatic CHF was rare (0.5 %). Compared to unaffected patients, those with a fall in LVEF were more likely to have hypertension, hyperlipidemia or coronary artery disease (CAD). Concomitant trastuzumab and anthracycline use was a risk factor (36 vs 9.5 % for anthracycline alone, p < 0.001). The median time from start of chemotherapy to reduced LVEF was 202 days (5–3008). On multivariate analysis, hypertension and use of trastuzumab remained independent predictors of LVEF fall. Acute recovery in LVEF was observed in 44 % of patients. LVEF changes from cancer therapies are frequent and hard to predict. Hypertension, hyperlipidemia and CAD are associated with LVEF decline. Acute recovery of LVEF is observed in those experiencing treatment-related cardiotoxicity. Attention to timely interruption of cardiotoxic chemo is recommended.

Background: The predominant breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), have similar recurrence and survival rates but differing patterns of metastatic recurrence. Methods: A retrospective review of breast cancers treated at an academic medical center from 1999 to 2012 was performed. Demographic, pathologic, treatment, and follow-up data were collected for 179 ILC and 358 IDC patients (1:2 stage-matched). The median follow-up was 4.7 years. Results: The baseline characteristics were similar in the two groups. ILC was more likely to be hormone-receptor-positive/HER2-negative and mammographically occult. The number of surgical resections, breast conservation rate, systemic treatment, and taxane use was similar between the groups. The overall recurrence rate was the same. ILC recurred more often in the abdominal cavity (24.3% in ILC vs. 4.1% in IDC, p = 0.001). The disease-free survival and overall survival were equal. On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not. Conclusions: Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes and survival. Our data suggest that enhanced surveillance and imaging might be useful in ILC.