Prognosis In Premenopausal Patients Research Articles

Low TINAGL1 expression is a marker for poor prognosis in breast cancer.

Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. The median follow-up period was 12.0years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

The impact of obesity and endocrine therapy on the prognosis of premenopausal women with hormone receptor-positive breast cancer: A single-institute retrospective study.

Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC. To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p=.0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p=.0086); however, a significant difference was not shown in patients who received TAM and OFS (p=.0921). High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.

Abstract P4-11-06: Effect of suppressed ovarian function on prognosis of premenopausal obese women with hormone receptor-positive breast cancer: A single-institute retrospective study

Abstract Background: Obesity is related to poor prognosis in pre- and postmenopausal patients with breast cancer. However, there is insufficient evidence regarding the optimal adjuvant hormone therapy for obese premenopausal women with hormone receptor-positive breast cancer. We examined the impact of ovarian function suppression (OFS) on the prognosis of obese women with primary hormone receptor-positive breast cancer. Methods: We retrospectively reviewed premenopausal women who received curative surgery for clinical stage I-III hormone receptor (HR)-positive breast cancer at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from January 2007 to December 2017. All patients were classified into five groups according to body mass index (BMI): underweight (UW), BMI <18.5 kg/m2; normal weight (NW), 18.5-24.9 kg/m2; obese 1 degree (OB1), 25.0-29.9 kg/m2; obese 2 degree (OB2), 30.0-34.9 kg/m2; and obese 3 degree (OB3), ≥35 kg/m2. The primary analysis was a comparison of breast cancer-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant hormonal therapy (with or without OFS). Secondary endpoints included overall survival (OS). Results: Overall, the total number of patients was 13,021 and the data of 3,380 patients were analyzed, which included patients who received adjuvant tamoxifen (TAM) without OFS (n = 1,836) or with OFS (n = 670). The median follow-up duration was 5.9 years (range, 0.2-12.9). The numbers of patients with UW, NW, OB1, OB2, and OB3 were 404 (12%), 2,482 (73%), 399 (12%), 78 (2%), and 17 (1%), respectively. Obesity was significantly associated with higher stage of breast cancer (p <0.0001). Nuclear grade of breast cancer in OB1-3 patients was significantly higher than that in UW/NW patients (p = 0.0323). BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = 0.0009). In OB1-3 patients who received TAM as adjuvant hormone therapy, BCSS was significantly worse than that in UW/NW patients (p = 0.0086); however, a significant difference was not shown in patients who received TAM and OFS (p = 0.0921). Multivariate analysis revealed that OB3 was an independent prognostic factor compared with NW in patients with stage II/III breast cancer (p = 0.0162).Conclusion: High BMI was associated with worse prognosis in premenopausal patients with HR-positive breast cancer. The negative impact of obesity might be canceled by adding OFS to TAM as adjuvant hormone therapy. Further studies are required to explore the adequate management of obese premenopausal patients. Citation Format: Yukinori Ozaki, Jun Masuda, Akemi Kataoka, Takahiro Kogawa, Tomomi Abe, Hidetomo Morizono, Lina Inagaki, Fumikata Hara, Toshimi Takano, Takayuki Ueno, Shinji Ohno. Effect of suppressed ovarian function on prognosis of premenopausal obese women with hormone receptor-positive breast cancer: A single-institute retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-06.

High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

27-hydroxycholesterol (27HC), synthesized from cholesterol by the enzyme CYP27A1, differentially impacts estrogen receptor positive (ER+) breast cancer (BC) cell growth depending on estrogen levels. This study examined the association between CYP27A1 expression and prognosis in a cohort of 193 premenopausal patients with lymph node-negative primary BC with limited exposure to adjuvant systemic cancer treatments. In multivariable analyses among patients with ER+ tumors, high CYP27A1 protein and mRNA expressions were associated with four- and eight-fold reductions in the incidence of distant recurrence-free survival events: HRadj = 0.26, 95% CI = 0.07–0.93 and HRadj = 0.13, 95% CI = 0.03–0.60, respectively. In vitro studies revealed that 27HC treatment potently inhibited ER+ BC cell proliferation under lipid-depleted conditions regardless of estradiol levels, transcriptionally mediated through the downregulation of ER signaling with a concomitant upregulation of cholesterol export. Importantly, if validated, these results may have implications for adjuvant treatment decisions in premenopausal patients, especially when de-escalation of therapy is being considered.

Nomogram Model of LNR Predicts Survival in Premenopausal Patients with Node-positive Luminal Breast Cancer.

The aim of this study was to assess the prognostic value of lymph node ratio (LNR) in premenopausal patients with luminal breast carcinoma. A total of 885 female patients who presented with axillary lymph node-positive luminal breast cancer between 2000 and 2009 were investigated. Using X-tile, we classified patients into low-, intermediate- and high-risk groups based on LNR. The Kaplan-Meier method was used to determine cumulative survival curves. Cox proportional hazards analyses were used to identify the factors that contributed to disease-free (DFS) and overall (OS) survival. The median age of patients was 42 years (range=21-58 years). A training set of 295 patients and a validation set of 590 patients were used to determine the optimal LNR cut-off points (0.20 and 0.63). DFS was 87.7%, 77.4% and 53.9% (p<0.001) and OS was 91.5%, 76.7% and 50.9% (p<0.0001) for the low- (≤0.20), intermediate- (0.21-0.63) and high-risk (>0.63) groups, respectively. The 10-year DFS and OS rates were significantly longer in the low-risk group than in the high-risk group. Nomogram analysis demonstrated that LNR contributed more compared to nodal stage in predicting both DFS and OS. We conclude that LNR strongly predicts prognosis in premenopausal patients with lymph node-positive luminal breast cancer.

Abstract P1-12-02: Effect of using LHRH analog during chemotherapy (CT) on premature ovarian failure and prognosis in premenopausal patients with early-stage, hormone receptor-positive breast cancer: The primary analysis of a randomized controlled phase III trial

Abstract Background: Whether administration of LHRH analog during CT in premenopausal patients with early-stage, hormone receptor-positive disease would reduce CT-induced premature ovarian failure (POF) is still controversial. Moreover, whether LHRH analog would influence the prognosis of patients is unknown yet. This randomized study is to evaluate whether administration of LHRH analog during CT would reduce POF and effect the prognosis of breast cancer. Methods: This is arandomized, controlled phase III clinical trial. Premenopausal patients age &amp;lt;46 with stage I-IIIA, ER/PR-positive BC to be treated with CT were randomized into two arms. Concurrent arm received CT with goserelin (GN) 3.6 mg SQ starting 0-7 days prior to the first CT dose, and after CT, the researchers determined whether continuous GN to 2-5years or cessation. Sequential arm received CT without GN, and after CT, the researchers determined GN 2-5 years immediately or after restoration of ovarian function or bilateral ovariectomy. Neoadjuvant CT was allowed. Five-year tamoxifen after CT was administered to all patients. The primary endpoint is POF, defined as amenorrhea for the prior 12 months and post-menopausal FSH or not assessed after last CT dose or last GN dose. Other endpoints include efficacy of neoadjuvant CT and relapse-free survival (RFS), defined as time to the first of these events: loco-regional recurrence, contralateral breast cancer or distant metastasis. Results: Between 2/09 and 5/13, the trial has finished enrollment, 216 patients were enrolled. The median age were 37.5 in combined arm (n=108) and 39 in sequential arm (n=108), respectively. The median follow-up time was 27.4 months and 25.7 months, respectively. 15 patients and 21 patients received neoadjuvant CT, respectively. There were no significant difference in age, tumor stage and CT regimens (p&amp;gt;.05). The median cycles of GN were 25, respectively. 47% had complete primary endpoint data. POF rate were 5/42 (11.9%) in the combined arm and 16/60 (26.7%) in the sequential arm. POF rate (and post-menopausal FSH) rate were 1/42 (2.4%) in the combined arm and 8/60 (13.3%) in the sequential arm. In neoadjuvant CT subgroup, each has 1 patient achieved pathological complete remission, and there was no significant difference in objective clinical response. There were 9 patients in the combined arm and 3 patients in the sequential arm had occured RFS events (including 2 and 0 deaths, respectively, OR=3.18, 95%CI:0.84-12.09, P=.075). Conclusions:LHRH analog administration with CT might be associated with less POF and did not affect the efficacy of neoadjuvant CT, however, had no RFS benefit, it may need longer follow-up. We will conduct an interim analysis in November 2014. Clinicaltrials.gov Registry Number: NCT01712893. Citation Format: Jian-Wei Li, Guang-yu Liu, Ke-Da Yu, Ya-jie Ji, Miao Mo, Li Lei, Jiong Wu, Gen-hong Di, Yi-feng Hou, Zhen Hu, Can-ming Chen, Zhen-Zhou Shen, Zhi-Ming Shao. Effect of using LHRH analog during chemotherapy (CT) on premature ovarian failure and prognosis in premenopausal patients with early-stage, hormone receptor-positive breast cancer: The primary analysis of a randomized controlled phase III trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-02.

Abstract P6-09-09: Body mass index and prognosis after breast cancer diagnosis in Japanese women

Abstract Background: Studies conducted mainly in Western countries have reported a relationship between body mass index (BMI) and prognosis among women with breast cancer. Only a few studies have been conducted in Japan so far because the percentage of high BMI is low. In the present retrospective study, we investigated the associations between BMI and the clinical characteristics and prognosis among breast cancer patients. Methods: We analyzed 1,744 breast cancer patients who started treatment between 2004 and 2012 at a single hospital in Japan. All patients with ductal carcinoma in situ, male breast cancer as well as metachronous and synchronous bilateral breast cancer were excluded. Median age was 57 years (range 23–91). The number of patients less than 50 years old was 496. World Health Organization BMI classifications were used: Underweight, less than18.5 kg/m2, n=157; Normal, 18.5–24.9 kg/m2, n=1181; Overweight, 25–29.9 kg/m2, n=316; and Obese, more than or equal to 30kg/m2, n=90. The Cox proportional hazards model was used to estimate hazard ratios for recurrence free survival (RFS) in relation to BMI classifications. Results: Median follow up interval was 4.2 years. During the follow-up period, 126 breast cancer recurrences were observed. BMI classification correlated with clinical tumor size (cT) significantly and BMI classification tended to correlate with lymph node metastases and estrogen receptor (ER) status. Among patients less than 50 years old, the RFS of those with BMI ≥25.0 kg/m2 was compared to that of patients with BMI &amp;lt;25.0 kg/m2. In multivariate analyses, BMI classification was one of the significant factors (p=0.02) along with lymph node metastases (p=0.0001) and ER status (p=0.04). However in patients aged 50 years or over BMI category was not a significant factor (p=0.12). Conclusions: It has been reported that higher BMI is a risk factor for breast cancer recurrence among postmenopausal patients. Our results suggest that higher BMI is also associated with an increased risk of breast cancer recurrence among premenopausal patients. It raises the possibility that maintaining an appropriate body weight improves the prognosis in premenopausal patients after they have been diagnosed. Citation Format: Toshinari Yamashita, Tomoyuki Aruga, Hiromi Miyamoto, Kazumi Horiguchi, Yayoi Honda, Nami Idera, Risa Goto, Katsumasa Kuroi. Body mass index and prognosis after breast cancer diagnosis in Japanese women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-09-09.

Impact of obesity and overweight in the prognosis of women diagnosed with non metastatic breast cancer in a Mexican cohort.

1607 Background: Mexico positions right up at the top with U.S. in worldwide rankings of the most obese countries. In addition, breast cancer (BrCa) is the main type of cancer among women in this country. Studies have shown inconsistent results regarding obesity as a prognostic factor for worse outcome. Methods: Our aim is to identify if overweight and obesity confer poor prognosis in non-metastasic BrCa patients (pts). We identified 1799 Hispanic women with newly diagnosed BrCa who attended the National Cancer Institute in Mexico from 2004-2008 and compared clinical and pathological features and overall survival (OS) between pts with a body mass index (BMI) &gt; or ≤ than 25. Results: The median age at diagnosis was 51 years. A BMI&gt;25 was found in 71% of pts. Postmenopausal women comprised 52%, and had a greater proportion of cases with a BMI&gt;25 than premenopausal pts (75% vs. 67%, p&lt;0.0001). Pts with BMI&gt;25 presented with more advanced TNM stages and nodal involvement than their counterparts (73% vs. 67%, p=0.005 and 76% vs. 71%, p=0.017; respectively). Overall prevalence of hormone-receptor (HR), triple-negative (TN) and HER2 positive disease was 62%, 23%, and 27%, respectively. Differences according to receptor status between pre and postmenopausal pts and BMI are shown in table. There was no difference in disease-free survival and OS according to overweight and obesity in the overall population, but when menopausal status was considered, premenopausal pts with BMI&gt;25 had a worse OS compared to pts with BMI&lt;25 (HR 1.6, p=0.037). This difference was not seen in the postmenopausal group. Conclusions: Obesity may influence BrCa outcomes via several hormonal and inflammatory mechanisms. In this study, overweight and obesity confer a poor prognosis in premenopausal patients, possibly related to excess estrogen availability and higher prevalence of TN BrCa. Therefore, overweight and obesity deserve additional attention to assess possible causal relationships that potentially could be modified to improve outcomes in premenopausal patients. [Table: see text]

Body mass index (BMI) is a predictor for response to neoadjuvant chemotherapy in women with localized breast cancer aged 35 years or younger

600 Objective: High BMI has been linked to poor outcome in patients with breast cancer. Evidence relating to obesity as a predictor for prognosis in premenopausal patients have been controversial. The aim of this study is to evaluate the impact of BMI on response to treatment and recurrence following neoadjuvant CT in young patients with breast cancer.> Method: In this study, we analyzed the impact of BMI on the outcome of 111 patients who received anthracycline and/or taxane-based neoadjuvant CT for localized breast cancer. Median age at diagnosis was 32 (22–35). Fifty six patients (50.5%) had stage II and 54 had stage III disease. Hormonal receptors were positive in 65 patients (58.6%) and HER-2/neu was overexpressed in 29 patients (26.1%). Pathologic evaluation revealed that 27 patients had (24.3%) had downstaging in axillary LN, while 13 (11.7%) showed complete regression both in the primary tumor and axillary LN following completion of chemotherapy. Patients were grouped in quartiles of BMI calculated prior to initiation of chemotherapy. >Results: After a median follow-up period of 26 months (3–94), 39 patients experienced recurrence (35.1%). Median overall (OS) and progression-free (PFS) survival rates at 5 years were 62.6 %±9.7 and 38.6%±8.1, respectively.Multivariate Cox regression analysis revealed pathologic response (OR:2.3, p=0.04) and recurrence (OR:108.7, p:0.047) as significant independent prognostic factors for PFS and OS, respectively. Lowest BMI quartile was significantly associated with lack of pathologic response to neoadjuvant chemotherapy compared to those with a larger body size (OR: 3.9, p=0.009). Conclusion: Obesity did not correlate with prognosis in young, premenopausal women with early breast cancer. However, patients within the lowest BMI quartile were less likely to respond to neoadjuvant anthracycline or taxane-based chemotherapy. Unresponsiveness to CT may account for the poor outcome in young premenopausal patients compared to older patients. The role of BMI on the outcome of this subset of patients should be validated further by larger prospective studies. No significant financial relationships to disclose.

Body mass index (BMI) is a predictor for response to neoadjuvant chemotherapy in women with localized breast cancer aged 35 years or younger

600 Objective: High BMI has been linked to poor outcome in patients with breast cancer. Evidence relating to obesity as a predictor for prognosis in premenopausal patients have been controversial. The aim of this study is to evaluate the impact of BMI on response to treatment and recurrence following neoadjuvant CT in young patients with breast cancer.> Method: In this study, we analyzed the impact of BMI on the outcome of 111 patients who received anthracycline and/or taxane-based neoadjuvant CT for localized breast cancer. Median age at diagnosis was 32 (22–35). Fifty six patients (50.5%) had stage II and 54 had stage III disease. Hormonal receptors were positive in 65 patients (58.6%) and HER-2/neu was overexpressed in 29 patients (26.1%). Pathologic evaluation revealed that 27 patients had (24.3%) had downstaging in axillary LN, while 13 (11.7%) showed complete regression both in the primary tumor and axillary LN following completion of chemotherapy. Patients were grouped in quartiles of BMI calculated prior to initiation of chemotherapy. >Results: After a median follow-up period of 26 months (3–94), 39 patients experienced recurrence (35.1%). Median overall (OS) and progression-free (PFS) survival rates at 5 years were 62.6 %±9.7 and 38.6%±8.1, respectively.Multivariate Cox regression analysis revealed pathologic response (OR:2.3, p=0.04) and recurrence (OR:108.7, p:0.047) as significant independent prognostic factors for PFS and OS, respectively. Lowest BMI quartile was significantly associated with lack of pathologic response to neoadjuvant chemotherapy compared to those with a larger body size (OR: 3.9, p=0.009). Conclusion: Obesity did not correlate with prognosis in young, premenopausal women with early breast cancer. However, patients within the lowest BMI quartile were less likely to respond to neoadjuvant anthracycline or taxane-based chemotherapy. Unresponsiveness to CT may account for the poor outcome in young premenopausal patients compared to older patients. The role of BMI on the outcome of this subset of patients should be validated further by larger prospective studies. No significant financial relationships to disclose.

Lack of correlation between timing of surgery in relation to the menstrual cycle and prognosis of premenopausal patients with early breast cancer

In a retrospective cohort of a randomised study of adjuvant endocrine, chemotherapy and chemo-endocrine therapy, we investigated the correlation between timing of mastectomy and relapse-free survival (RFS) and overall survival (OS) in 721 premenopausal patients with early breast cancer. The median follow-up was 10.1 years (range: 6.1–19.1 years). We grouped the patients by three kinds of classification according to Badwe, Senie, and Hrushesky. The logrank test after the Kaplan–Meier curves showed that there were no significant differences between the categorised menstrual phase in cycle and RFS or OS, except for RFS using Badwe's classification, where the patients whose timing of operation was in the follicular phase had a better RFS compared with those in the luteal phase. These were confirmed by the Cox proportional hazard model. These results suggest that a positive result might be a chance finding, dependent upon the cut-off levels in the menstrual cycle.

P51 Lack of correlation between menstrual phase during operation and prognosis of premenopausal patients with early breast cancer in a randomized study of adjuvant chemo-endocrine therapy

P51 Lack of correlation between menstrual phase during operation and prognosis of premenopausal patients with early breast cancer in a randomized study of adjuvant chemo-endocrine therapy

Prognostic significance of dna‐ploidy in a series of 690 primary breast cancer patients

Flow cytometric DNA-ploidy measurements were performed on paraffin-embedded and fresh tumor specimens from 690 patients with Stage I-III breast cancer. The conventional classification of DNA-ploidy (diploid versus aneuploid) was compared with a division of tumor ploidy into 5 classes based on DNA index (DI) range. The DI-classification showed a better correlation with tumor size and TNM stage than the conventional classification. Aneuploidy was associated with an impaired survival and distant relapse-free survival (p = 0.02) but the DI-classification improved the discrimination between different prognostic groups of patients. In general, this indicated a more aggressive phenotype for tumors evolved via polyploidization. Hyper-tetraploidy (DI greater than 2.10) indicated a very poor prognosis in pre-menopausal patients. No prognostic effect of aneuploidy and DI-class was found in node-negative and TI patients. Cox multivariate regression analysis showed that aneuploidy was an additional prognostic factor to nodal status (I less than or equal to N less than or equal to 3, N greater than 3 vs. N = 0) and tumor size (T2-4 vs. TI) for overall and distant relapse-free survival. Subdivision according to DI-class did not improve the prognostic power of DNA-ploidy due to stronger correlations with established prognostic factors.