Treatment-induced menstrual changes in very young (<35 years old) breast cancer patients

Summary Purpose To evaluate the treatment-induced menstrual changes in very young (< 35 years old) breast cancer patients. Methods and materials We retrospectively examined the clinical records of 160 patients, ranging in age from 18 to 34 years old (median age, 32 years), treated between June 1992 and December 2002. One hundred twenty patients underwent mastectomy and 40 underwent breast conserving surgery. Postoperatively, 80 patients were treated with alkylating agent-based chemotherapy regimens (CMF) and 80 with anthracycline-based regimens (AD). In addition, 57 patients received adjuvant radiotherapy, and 77 received anti-estrogen therapy. Treatment-induced menstrual changes and present menstrual status were evaluated from hospital records and by one-to-one interviews. The median follow-up period was 54 months (range, 29–156 months). Results Treatment-induced menstrual change (amenorrhea) was occurred in 59 (36.9%) patients, 25 (31.3%) of those treated with CMF and 34 (42.5%) with AD (p=0.142). Amenorrhea occurred after a median 2 cycles of chemotherapy (range, 1–6 cycles). Menstruation resumed in 49 (83.1%) patients, 20 (80%) of those treated with CMF and 29 (85.3%) with AD (p=0.6). Median time to resumption of menstruation was median 3.5 months (range, 1–18 months) after amenorhrea. Disease recurred in 10 (16.9%) patients who experienced treatment-induced menstrual changes and in 18 (17.8%) of those who did not (p=0.89). Conclusion Although the overall incidence of treatment-induced menstrual change in breast cancer patients under age 35 was similar to that reported elsewhere, the rate of recovery from these change is higher. We observed no difference between CMF and AD treated patients in rates of amenorrhea or recovery from these changes.     

A long-term retrospective comparative study of the oncological outcomes of 598 very young (≤35 years) and young (36–45 years) breast cancer patients

BackgroundBreast cancer diagnosed in very young women (VYWBC; ≤35 years) and young women (YWBC; 36–45 years) tends to be heterogeneous. The current study aimed to compare the clinicopathological characteristics and long-term clinical outcomes between YWBC and VYWBC subgroups.Patients and methodsThe institutional prospectively led database was retrospectively analysed from 2000 to 2014 at the National Institute of Oncology, Hungary. A total of 297 patients were assigned to the VYWBC group, and 301 patients were assigned to the YWBC group.ResultsThe median follow-up period was 69 months for the VYWBC group and 79 months for the YWBC group. Significant differences were observed based on breast cancer subtype. The proportion of Triple-negative and ER-negative patients was higher in the VYWBC group than in the YWBC group (P = 0.00008). The incidence of distant metastasis was significantly higher in the VYWBC group (P = 0.01). Significant differences in the frequency of chemotherapy (P = 0.049) and endocrine therapy (P = 0.037) were observed between the two groups. The YWBC group exhibited significantly better overall survival (OS) and disease-free survival (DFS) rates than did the VYWBC group (P = 0.00005 and P = 0.00004, respectively).ConclusionBreast cancers in VYWBC are biologically different from those in YWBC and tend to be more aggressive. Younger age was associated with worse OS and DFS. Young women with breast cancer should be subgrouped into VYWBC and YWBC populations, and these subgroups should be targeted by specialized clinical trials and further investigations.     

Observations with alpelisib in older patients (≥ 65 year of age) with breast cancer in a non-clinical trial setting

Breast Cancer Research and Treatment - Alpelisib is newly-available breast cancer agent that targets PIK3 mutations and confers a somewhat unusual adverse event profile. This study focused on older...     

Relationship between age at diagnosis and outcome of premenopausal breast cancer: age less than 35?years is a reasonable cut-off for defining young age-onset breast cancer

Previous studies have reported significantly worse outcomes in younger women with breast cancer. The cut-off for young age differed between studies and it is unclear whether the survival-age relationship is a linear function across age in premenopausal women. We analyzed data on 9,885 breast cancer patients aged ≤50 years who entered the Korean Breast Cancer Society Registration Program between 1992 and 2001. Overall survival data were compared among age groups. The median follow-up duration was 74.4 months. Of all patients, 351 were aged <30 years (Group I), 1,092 were aged 30–34 years (Group II), 2,087 were aged 35–39 years (Group III), and 6,354 were aged 40–50 years (Group IV). In univariate and multivariate analyses, Group I patients showed a worse outcome than Group II patients, and Group II patients showed a worse outcome than Group III patients. Interestingly, the survival rates of Group III and Group IV patients did not differ significantly. This survival trend according to age group was not found in the subgroup of patients with hormone receptor-negative tumors. In patients aged <35 years, the risk of death rose by 5% for every 1-year reduction in age, whereas there was no significant change in death risk with age in patients aged 35–50 years. We show that risk of death from breast cancer increases sharply in women younger than 35 years. This suggests that age less than 35 years is a reasonable cut-off for defining young age-onset breast cancer.     

Characteristic features and usefulness of MRI in breast cancer in patients under 40 years old: correlations with conventional imaging and prognostic factors

Background

The purpose of this study was to evaluate the characteristic features and usefulness of magnetic resonance imaging (MRI) of breast cancer in women under 40 years old that are correlated with conventional imaging and prognostic factors.

Methods

We performed a retrospective review of the clinical, radiological and pathological features of patients under 40 years old with breast cancer at our institution between October 2007 and December 2010. A total of 99 women were included.

Results

The most common MRI findings were a mass or multiple masses (82.8 %) similar to those observed with mammography (50.5 %) and ultrasonography (90.9 %). The sensitivity of both MRI and ultrasonography for detecting a primary breast lesion was 100 % compared to 87.4 % with mammography. After preoperative MRI, the surgical plan changed in 35.7 %. The rim enhancement of the mass was a significant and independent predictor of a higher histological grade (p = 0.005), negative expression of ER (p = 0.01) and PR (p = 0.02). The clumped enhancement of the non-mass lesion was also associated with positive LN metastasis (p = 0.04).

Conclusion

Breast cancer in women under 40 years old frequently presents as suspicious masses on both conventional imaging and MRI. Ultrasonography and MRI both showed excellent sensitivities that were better than those of mammography in young women with dense breasts. Additionally, MRI can play an important role in preoperative planning, and some BI-RADS MRI features can be used to predict breast cancer prognosis in this age group.     

Individual radiosensitivity in a breast cancer collective is changed with the patients’ age

Background

Individual radiosensitivity has a crucial impact on radiotherapy related side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity depending on the patients’ age.

Materials and methods

Peripheral blood samples were obtained from 129 individuals. Individual radiosensitivity in 67 breast cancer patients and 62 healthy individuals was estimated by 3-color fluorescence in situ hybridization.

Results

Breast cancer patients were distinctly more radiosensitive compared to healthy controls. A subgroup of 9 rather radiosensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radiosensitive than younger or older patients.

Conclusions

In the breast cancer collective a distinct resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Preliminary results indicate that especially in the range of age 40 to 50 patients with an increased radiosensitivity are more frequent and may have an increased risk to suffer from therapy related side effects.     

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case–control study

Purpose

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer.

Methods

Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical–pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical–pathologic features was assessed using Cox proportional hazard models.

Results

Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages.

Conclusion

Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

     

Phase II study of S-1 plus oxaliplatin 130 mg/m<Superscript>2</Superscript> in Japanese patients with advanced gastric cancer

Purpose

Although oxaliplatin 130 mg/m² every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m² (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer.

Methods

Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0–1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥?80% relative dose intensity of oxaliplatin.

Results

Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8–86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1–19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9–8.5) and 13.1 months (95% confidence interval 7.4–19.0), respectively.

Conclusion

Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.

     

Comparison of clinicopathologic features and survival in young American women aged 18–39 years in different ethnic groups with breast cancer

Background:

Ethnic disparities in breast cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have assessed differences specifically between Asians American(s) and other ethnic groups, particularly among Asian American(s) subgroups, in women aged 18–39 years.

Methods:

The Surveillance, Epidemiology, and End Results database was used to identify women aged 18–39 years diagnosed with breast cancer from 1973 to 2009. Incidence rates, clinicopathologic features, and survival among broad ethnic groups and among Asian subgroups.

Results:

A total of 55 153 breast cancer women aged 18–39 years were identified: 63.6% non-Hispanic white (NHW), 14.9% black, 12.8% Hispanic-white (HW), and 8.7% Asian. The overall incidence rates were stable from 1992 to 2009. Asian patients had the least advanced disease at presentation and the lowest risk of death compared with the other groups. All the Asian subgroups except the Hawaiian/Pacific Islander subgroup had better DSS than NHW, black, and HW patients. Advanced tumour stage was associated with poorer DSS in all the ethnic groups. High tumour grade was associated with poorer DSS in the NHW, black, HW, and Chinese groups. Younger age at diagnosis was associated with poorer DSS in the NHW and black groups.

Conclusion:

The presenting clinical and pathologic features of breast cancer differ by ethnicity in the United States, and these differences impact survival in women younger than 40 years.     

Pregnancy-associated breast cancer: a case— control study in a young population with a high-fertility rate

Pregnancy-associated breast cancer (PABC) is not a rare event. The association frequently imposes a management challenge. We intended to review the clinical features, therapy, and outcome of patients with PABC seen at a single institution over a five-year period and to compare those with that seen in a matched control group. Data of all patients with PABC diagnosed during pregnancy were retrospectively reviewed (Group I). For each patient in Group I, three matched controls with breast cancer without pregnancy were identified (matched for age, stage, and year of diagnosis, Group II). 72 patients in Group I and 216 in Group II were identified. Their median age was similar (34 vs 35 y, respectively). The median number of prior pragnancies for patients in Groups I and II was 5. Patients had shorter duration of symptoms prior to diagnosis as compared with their controls (5.6 vs 9.4 months,P<0.0001). 3%, 31%, 40%, and 26% of patients had Stage I to IV, respectively. A pattern that was similar to that seen in our breast cancer population. Pregnancy was terminated in 34 patients (47%), while 38 (53%) had normal spontaneous vaginal delivery. 47 patients in Group I had surgery; 37 (52%) had modified radical mastectomy and 10 (14%) had conservative surgery. In 37 patients surgery was performed after termination of pregnancy and 10 had surgery performed during pregnancy. The median number of positive lymph nodes in Group I was 4 as compared with 2 for patients in Group II. No patients in Group I had systemic chemotherapy during first trimester, while only 4 (6%) and 3 (4%) received adjuvant or neoadjuvant during second and third trimester, respectively. No congenital malformation in the newborns was diagnosed. None of the patients in Group I received radiotherapy during pregnancy.     

Occupation and breast cancer in women 20–44 years of age (United States)

Objective: To examine the relation between breast cancer risk and job history among women 20–44 years of age who participated in a multi-center, population-based, case–control study. Methods: Participants consisted of women newly diagnosed with breast cancer (1642) and controls identified by random-digit dialing (1494). Details about the three longest jobs were collected and coded by an industrial hygienist. Odds ratios and 95% confidence intervals were calculated and adjusted for age, study site, and other breast cancer risk factors. Results: Several occupational and industrial categories were found to influence breast cancer risk. Stratification of the study population by parity revealed differences in breast cancer risk between the two groups for several occupational categories, including teachers, librarians or counselors (increased risk only among parous women) and natural scientists and mathematicians (decreased risk only among nulliparous women). Conclusions: This is among the first population-based case–control studies to examine occupational history and breast cancer risk in young women, with the ability to consider a wide array of potential confounders, including reproductive characteristics. This study provides further evidence of an increased breast cancer risk for several occupations and industries. Other findings were not as strongly supported by previous investigations.     

Long-term gemcitabine administration in heavily pretreated Japanese patients with metastatic breast cancer: additional safety analysis of a phase?II study

Background

Recently gemcitabine has been approved for treatment of metastatic or recurrent breast cancer in Japan; however, no systematically investigated safety study of long-term gemcitabine monotherapy has been reported despite its wide use globally for multiple indications.

Patients and methods

In a previously reported phase?II study, 62 Japanese metastatic breast cancer patients with progressive disease after treatment with anthracyclines and taxanes were treated with gemcitabine 1250?mg/m² on days?1 and 8 of a 21-day cycle. For this report we re-analyzed the safety profiles for the 13 patients who received 10 or more cycles of the therapy.

Results

Most grade?3/4 adverse events seen after 10 cycles were hematological toxicities. These were similar to those seen before the 10th cycle; however, 2 patients showed grade?3 nonhematological severe adverse events including acute cardiac failure and loss of consciousness. All adverse events were reversible and manageable. One patient received gemcitabine treatment for up to 54 cycles without unmanageable toxicities.

Conclusion

Toxicities seen in long-term gemcitabine treatment were reversible and manageable in this setting of heavily pretreated Japanese metastatic breast cancer patients.     

A pilot multi-institutional study to evaluate the accuracy of a supine MRI based guidance system,the Breast Cancer Locator™, in patients with palpable breast cancer

BackgroundEvaluate whether the Breast Cancer Locator™ (BCL), a novel guidance system based on supine MRI images, can be safely and effectively deployed by several surgeons at multiple sites.MethodsPatients with palpable breast cancer underwent supine MRI at their local institution. A three dimensional (3D) digital image of the tumor in the breast was derived from supine MRI images and used to generate 1) an interactive 3D virtual image of the tumor in the breast (Visualizer) and 2) a plastic bra-like form that allowed the surgeon to place a central wire and bracketing wires in the breast (BCL). The primary objective was to determine the proportion of patients who had the central localization wire deployed within the cancer on specimen mammogram.ResultsFourteen patients were enrolled at 4 different sites by 6 surgeons. BCLs were successfully manufactured for all patients. The central wire was deployed within the tumor on specimen mammogram in 12 of the 13 patients who had a central wire placed (92%). The cancer was excised with negative margins in 14/14 cases (100%). No adverse events occurred.ConclusionsSupine MRI image acquisition was accomplished successfully across multiple sites. Multiple surgeons utilized the BCL system to localize cancers accurately and safely.     

Effect of screening mammography on cumulative survival of Japanese women aged 40–69 years with breast cancer

Background

The effectiveness of screening mammography (MMG) has mainly been demonstrated by studies in western countries. This study was conducted to evaluate cumulative survival and the risk of breast cancer death among Japanese women aged 40–69 years with screening-detected and interval breast cancer divided into three groups: MMG with clinical breast examination (CBE), CBE alone, and self-detection.

Methods

By matching a list of 126,537 women (358,242 person-screenings) who participated in the Miyagi Cancer Society Screening program between 1 April 1995 and 31 December 2002 with the Miyagi Prefectural Cancer Registry, 429 MMG with CBE, 522 CBE, and 3,047 self-detected cases were included in this study. Follow-up was performed until the date of death or 31 December 2007. Survival was estimated by the Kaplan–Meier method. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for breast cancer death.

Results

Five-year survival for women in the MMG with CBE, CBE, and self-detection groups was 96.8, 92.7, and 86.6 %, respectively. The HR (95 % CI) for breast cancer death was 2.38 (0.72–7.94) among CBE-screened and 4.44 (1.42–13.89) among self-detected cases for women aged 40–49 years, but was 3.00 (1.63–5.50) among CBE-screened and 4.51 (2.69–7.56) among self-detected cases for women aged 50–69 years relative to cases screened by use of MMG with CBE.

Conclusions

In terms of the survival and risk of breast cancer death, MMG with CBE may be more effective than MMG alone or self-detection for Japanese women aged 40–69 years.