Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

PURPOSE: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes. METHODS: This was a national, multi-site, retrospective observational study, including PABC patients treated in 12 oncology institutions from August 2001 to January 2020. Data extracted included information on patient demographics, tumour biology, staging, treatments, and maternal/foetal outcomes. Survival data for an age-matched breast cancer population over a similar time period was obtained from the National Cancer Registry of Ireland (NCRI). Standard biostatistical methods were used for analyses. RESULTS: We identified 155 patients-71 (46%) were gp-PABC and 84 (54%) were pp-PABC. The median age was 36 years. Forty-four patients (28%) presented with Stage III disease and 25 (16%) had metastatic disease at diagnosis. High rates of triple-negative (25%) and HER2+ (30%) breast cancer were observed. We observed an inferior 5-year overall survival (OS) rate in our PABC cohort compared to an age-matched breast cancer population in both Stage I-III (77.6% vs 90.9%) and Stage IV disease (18% vs 38.3%). There was a low rate (3%) of foetal complications. CONCLUSION: PABC patients may have poorer survival outcomes. Further prospective data are needed to optimise management of these patients.

Oxaliplatin-related dysphagia: Mixed-methods study.

OBJECTIVES: To evaluate participant-reported atypical dysphagia symptoms and their association with oxaliplatin treatment. METHODS: This observational study recruited 73 adults with solid tumours outside the head, neck or upper gastrointestinal tract. All had dysphagia, were in hospital or hospice and were treated by Medical Oncology, Radiation Oncology or Palliative Care. Participants reported their experiences of swallowing difficulties by semistructured interview. Oral Health Assessment Tool was used to ensure swallow difficulties were not due to mucositis. Responses were transcribed and analysed by content analysis. Atypical difficulties were examined for association with oxaliplatin treatment by Fischer's Exact. RESULTS: Oxaliplatin treatment was associated with three unusual dysphagia symptoms: problems with cold or hot bolus (p=0.01), pins and needles (p=0.001) and throat spasm (p=0.035). Carbonation was problematic for one participant. Chemotherapy commencement coincided with swallow problem onset for 67%. Dysphagia symptoms were unrelated to mucositis (p=0.165). CONCLUSIONS: Swallowing difficulties in oxaliplatin-treated patients are atypical and attributable to chemotherapy commencement. Previous research suggests that dysphagia is triggered by cold exposure, but hot and carbonated boluses also caused problems here. Dysphagia symptoms and triggers should be studied more fully to help patients safely enjoy their meals and prevent food avoidance, which could exacerbate malnutrition.

Dysphagia in Solid Tumors Outside the Head, Neck or Upper GI Tract: Clinical Characteristics.

CONTEXT: Dysphagia is common in cancer, but underlying pathophysiology and manifestations within patients are unknown. OBJECTIVES: To examine dysphagia characteristics in those with solid malignancies outside the head, neck and upper gastrointestinal tract. METHODS: Seventy-three individuals with dysphagia (46 male, 27 female, aged 37-91) were recruited from a parent trial conducted in two acute hospitals and one hospice. Cranial nerve function, Oral Health Assessment Tool (OHAT), Mann Assessment of Swallowing Ability (MASA) and Functional Oral Intake Scale (FOIS) evaluated swallow profile. RESULTS: Only 9/73 (12%) had documented dysphagia prior to study enrollment. MASA risk ratings found n=61/73 (84%) with dysphagia risk and n=22/73 (30%) with aspiration risk. Food texture modification was required for n=34/73 (47%), fluid texture modification for n=1/73 (1%). Compensatory strategies for food were needed by n=13/73 (18%) and for fluids by n=24/73 (33%). Cranial nerve deficits were present in n=43/73 (59%). Oral health problems were common, with xerostomia in two-thirds. Worse dysphagia on MASA was associated with disease progression, affecting hospice, and palliative care the most. Worse performance status was indicative of poorer MASA raw score (P<0.001, OR 2.2, 95% CI 1.5-3.4), greater risk of aspiration (P=0.005, OR 2.1, 95% CI 1.3-3.6) and lower FOIS (P=0.004, OR 2.0, 95% CI 1.2-3.2). CONCLUSION: Dysphagia management in those with cancer requires robust assessment to uncover clinically important needs like food texture modification and safe swallowing advice. Better assessment tools should be developed for this purpose. Oral health problems should be routinely screened in this population since they exacerbate dysphagia.

Triple-negative breast cancers are increased in black women regardless of age or body mass index.

INTRODUCTION: We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis. METHODS: We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression. RESULTS: 415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08). CONCLUSIONS: Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.

Treatment completion, treatment compliance and outcomes of old and very old patients treated by dose adapted stereotactic ablative radiotherapy (SABR) for T1-T3N0M0 non-small cell lung cancer.

AIM: This is a retrospective single-institution review of the treatment completion and clinical outcomes of patients aged 75 and older, treated with stereotactic ablative body radiotherapy (SABR) for T1-T3 N0 M0 non-small cell lung cancer (NSCLC). METHODS: From April 2008 to September 2015, 200 patients, aged 75-93, received respiratory-managed, intensity-modulated-based SABR. Dose fractionation was risk-adapted and delivered in 2-3 weekly treatments. Treatment completion, local control, overall survival and treatment-related toxicities were evaluated. RESULTS: All patients completed the prescribed SABR course. However, 29 patients required interruption of at least one fraction of SABR and optimization of pain control before continuation of the fraction. Median follow-up was 20.9 months. The median OS was 31.6 months with 1-,3-year survival rates of 80.7%, and 44.4% respectively. Local control at 1- and 3- years were 97.6%, 83.5% respectively. Treatment was well-tolerated. However, there were two (1%) G5 (fatal) toxicities: one acute sudden dyspnoea of unknown cause and one late SABR-related haemoptysis. No statistically significant differences in outcomes/toxicities were observed between old (75-84 years old) and very old patients (>85 years old). CONCLUSIONS: Old and very old patients can successfully complete SABR for NSCLC, with good local control, survival and acceptable toxicity. Old patients might require increased supportive care for successful treatment delivery.

Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose.

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established. Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome. Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival. Results: The median follow- up time for the entire cohort was 10.33 months (1.25-97.28). The overall median survival was 12.5months (95%CI = 5.8-19.2), with 53.3%, and 35.8% surviving at 1- and 2- years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI = 1.4-6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12-16 Gy can expect shorter LPFS than those receiving 18-20 Gy (HR = 1.7, 95% CI = 1.0-2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5-4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival. Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

Dysphagia Prevalence and Predictors in Cancers Outside the Head, Neck, and Upper Gastrointestinal Tract.

CONTEXT: Dysphagia is usually associated with malignancies of the head, neck, and upper gastrointestinal tract but also occurs in those with tumors outside anatomic swallow regions. It can lead to aspiration pneumonia, malnutrition, reduced quality of life, and psychosocial distress. No studies have yet reliably described dysphagia prevalence in those with malignancies outside anatomic swallow regions. OBJECTIVE: The objective of this study was to establish the prevalence and predictors of dysphagia in adults with solid malignancies outside the head, neck, and upper gastrointestinal tract. METHODS: A cross-sectional, observational study using consecutive sampling was conducted. There were 385 participants (mean age 66 ± 12 years) with 21 different primary cancer sites from two acute hospitals and one hospice. Locoregional disease was present in 33%, metastatic in 67%. Dysphagia was screened by empirical questionnaire and confirmed through swallow evaluation. Demographic and clinical predictors were determined by univariate and multivariate binary regression. RESULTS: Dysphagia occurred in 19% of those with malignancies outside anatomic swallow regions. Prevalence was 30% in palliative care and 32% in hospice care. Dysphagia was most strongly associated with cough, nausea, and worse performance status. It was also associated with lower quality of life and nutritional difficulties. CONCLUSION: Dysphagia was common and usually undiagnosed before study participation. It occurred at all disease stages but coincided with functional decline. It may therefore represent a cancer frailty marker. Oncology and palliative care services should routinely screen for this symptom. Timely dysphagia identification and management may improve patient well-being and prevent adverse effects like aspiration pneumonia and weight loss.

Patients with colorectal lung oligometastases (L-OMD) treated by dose adapted SABR at diagnosis of oligometastatic disease have better outcomes than patients previously treated for their metastatic disease.

AIM: To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease. METHODS: This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated. RESULTS: Median follow-up was 22.9±15.5 months (range: 2.6-68.6). For the entire cohort, LC was observed for 76.6% of the target lesions; the 2- year OS and PFS were 77% and 28 % respectively. After a median of 7.9 months from SABR, 39 patients presented a first progression. In univariate analysis, patients with multiple recurrences prior to SABR (p=0.001) and those who received chemotherapy for metastatic progression (p=0.014) had poorer PFS from time of SABR. Median PFS for patients with no prior treatment for L-OMD vs. prior chemotherapy +/- local treatment vs. local treatment only was: not reached vs. 8.83 (± 2) vs. 32.5 (±2.75) months. The main pattern of first progression was out of field progression: in-field progression alone occurred in 7 patients (12%) and with synchronous regional/distant progression in 10 patients (17%. In all patients, chemotherapy was withheld until progression post-SABR. Treatment was well tolerated; only one patient experienced grade 3 bronchial toxicity, three months after completion of SABR. CONCLUSIONS: SABR achieves high rates of local control with limited toxicities in patients with lung oligometastatic disease from a colorectal primary. This retrospective data indicates that patients with newly diagnosed lung oligometastatic disease may be safely treated with SABR as first treatment, with chemotherapy held in reserve. In heavily pretreated patients, SABR may allow patients a treatment break from systemic therapy, which may be beneficial both psychologically and physically. Future randomized SABR studies should evaluate sequencing of chemotherapy, the role of immunotherapies, and the quality of life of patients undergoing SABR.

Risk of decline in upper-body function and symptoms among older breast cancer patients.

BACKGROUND: Decline in upper-body function and development of upper-body symptoms are adverse effects of breast cancer therapy and may affect functional independence, particularly among older survivors. The long-term risks and predictors are poorly understood. OBJECTIVE: To characterize the risk of decline in upper-body function and development of symptoms over 4 years of follow-up. DESIGN: We used a prospective cohort design. PARTICIPANTS: Six hundred and forty-four early stage breast cancer patients 65 years old or older at surgery enrolled in Rhode Island, North Carolina, Minnesota, and Los Angeles between 1996 and 1999. MEASUREMENTS: Upper-body function and symptoms were self-reported at baseline, 6, 15 months, and annually thereafter to 51 months after surgery. RESULTS: One half of the participants had a decline in upper-body function and one-quarter developed upper-body symptoms. Breast cancer patients were 5-fold more likely to have a decline in upper-body function over 4 years of follow-up than a similar cohort without breast cancer. Better baseline mental health protected against a decline in upper-body function (odds ratio [OR]=0.93, 95% confidence interval [CI] 0.88 to 0.97 for 8-point higher mental health index). Baseline obesity (OR for body mass index [BMI] > or =30 kg/m2 vs <30 kg/m2=2.5, CI=1.6 to 4.0) and axillary node dissection (OR for axillary dissection vs not=3.9, CI=1.1 to 14) predicted the development of upper-body symptoms. CONCLUSIONS: Primary care physicians should address upper-body function and symptoms with older breast cancer patients, and inform them that these complications of breast cancer treatment are common.

Non-small-cell lung cancer: unusual presentation in the gluteal muscle.

Lung cancer is one of the most commonly diagnosed cancers in both men and women worldwide. It is also one of the most common forms of cancer in Ireland, accounting for about 20% of all deaths from cancer each year. Early detection of lung cancer is infrequent, and most cases are not diagnosed and treated until they are at an advanced stage. Distant metastases in lung cancer commonly involve the adrenal glands, liver, bones, and central nervous system; they are only rarely seen in the skeletal system. We report a rare case of metastasis to the gluteal muscle as the initial presentation of lung cancer.

Adherence to tamoxifen over the five-year course.

PURPOSE: To estimate the proportion of older women who fail to complete 5 years of tamoxifen therapy and to identify predictors of non-adherence. PATIENTS AND METHODS: We followed 462 women 65-years-old or older with stage I-IIIA breast cancer diagnosed in four US regions between 1996 and 1999 and who initiated tamoxifen therapy. We interviewed patients annually to assess tamoxifen adherence and collected information about predictors of adherence by medical record review, patient interview, and physician questionnaire. RESULTS: Thirty-one percent of patients who started tamoxifen failed to complete the recommended 5-year course. Patients who had initial severe side effects [hazard ratio (HR) per side effect=1.2, 95% confidence interval (CI) 0.97, 1.5] or developed them (HR per new side effect=1.3, 95% CI 1.0, 1.6) were more likely to discontinue. Patients with more prescription medications at baseline were less likely to discontinue (HR per baseline prescription equaled 0.90, 95% CI 0.81, 0.99), whereas patients who added a prescription were more likely to discontinue (HR per new prescription equaled 1.2, 95% CI 1.0, 1.4). Patients with positive views of tamoxifen at baseline (HR for a 10-point higher score=0.93, 95% CI 0.83, 1.0) and an improving view over follow-up (HR for a 10-point positive change=0.93, 95% CI 0.87, 1.0) were less likely to discontinue. CONCLUSION: Five years of tamoxifen confers a significant benefit beyond 1-2 years of tamoxifen, so physicians should ask patients about side effects, other prescriptions, and beliefs about tamoxifen and should educate them about the benefits of completing adjuvant therapy.