Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

Download Full-text

Management of early-stage breast cancer: Are we headed in the right direction?

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.284 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 284-284

Author(s):

U. Zurawska ◽

D. A. Baribeau ◽

C. Victor ◽

S. Giilck ◽

A. Florescu ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Histological Grade ◽

Growth Factor Receptor ◽

Early Stage Breast Cancer ◽

Her2 Positive ◽

Cancer Subtypes ◽

Excellent Outcome ◽

Hormone Receptor Positive ◽

The Right

284 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.

Download Full-text

The prognostic significance of early stage lymph node positivity in operable invasive breast carcinoma: number or stage

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-200755 ◽

2012 ◽

Vol 65 (7) ◽

pp. 624-630 ◽

Cited By ~ 9

Author(s):

Emad A Rakha ◽

David Morgan ◽

Douglas Macmillan

Keyword(s):

Breast Cancer ◽

Prognostic Value ◽

Independent Predictor ◽

Early Stage ◽

Histological Grade ◽

Tumour Size ◽

Prognostic Significance ◽

Absolute Number ◽

Consecutive Series ◽

Cancer Specific Survival

AimThe earlier detection of breast cancer through mammographic screening has resulted in a shift in stage distribution with patients who are node-positive tending to present with a lower number of positive lymph nodes (LN). This study aims to assess the prognostic value of absolute number of positive nodes in the pN1 TNM stage (1–3 positive LN) and whether the prognostic value of the number of nodes in this clinically important stage justifies its consideration in management decisions.MethodsThis study is based on a large and well-characterised consecutive series of operable breast cancer (3491 cases), treated according to standard protocols in a single institution, with a long-term follow-up.ResultsLN stages and the absolute number of LN are associated with both breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). In the pN1 stage, patients with three positive LN (14% of pN1) show shorter BCSS (HR=1.9, (95% CI 1.3 to 2.6)) and shorter DMFS (HR=2.2, (95% CI 1.6 to 2.9)) when compared with one and/or two positive nodes. This effect is noted in the whole series as well as in different subgroups based on tumour size (pT1c and pT2), histological grade (grade 2 and 3), vascular invasion and oestrogen receptor status (both positive and negative). Multivariable analyses showed that three positive LN, compared with one and two positive LN, are an independent predictor of shorter BCSS and DMFS.ConclusionThe number of LN in the pN1 stage yielded potentially informative risk assignments with three positive LN providing an independent predictor of poorer outcome.

Download Full-text

Survival Outcome and Impact of Chemotherapy in T1 Node-Negative Triple-Negative Breast Cancer: A SEER Database Analysis

Journal of Oncology ◽

10.1155/2020/8880727 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Jingyi Zhang ◽

Wenna Wang ◽

Jiayu Wang ◽

Yang Luo ◽

Shanshan Chen ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Large Scale ◽

Triple Negative ◽

Survival Rates ◽

Seer Database ◽

Cancer Specific Survival ◽

Small Tumor ◽

Significant Difference

Objective. Although triple-negative breast cancer (TNBC) has been considered to be an aggressive disease, the outcome of small-tumor (T1abcN0M0) TNBC and the effect of adjuvant chemotherapy on TNBC survival remain controversial. Methods. We identified 4565 T1abcN0M0 TNBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. After propensity score matching (PSM), 3214 patients were finally analyzed. Survival rates were compared among T1a, T1b, and T1c patients and between patients with and without adjuvant chemotherapy. Results. We classified 424, 1040, and 3101 cases as T1a, T1b, and T1c TNBC, respectively. A total of 2760 (60.5%) patients received adjuvant chemotherapy, accounting for 25.5%, 56.0%, and 66.8% of T1a, T1b, and T1c patients, respectively. Rates of 5-year breast cancer-specific survival (BCSS) for T1a, T1b, and T1c patients receiving chemotherapy were 97.8%, 94.1%, and 94.5%, respectively, compared with 97.2%, 94.0%, and 89.9% in patients without chemotherapy. Patients receiving adjuvant chemotherapy had higher 5-year BCSS (94.5% vs. 89.9%, P = 0.004) in the T1c subgroup, but no significant difference was detected in T1a or T1b patients due to adjuvant chemotherapy. Conclusion. Small-tumor TNBC showed very good prognosis. Adjuvant chemotherapy improved prognosis in T1c TNBC cases to a greater extent than in T1a and T1b patients. More large-scale clinical trials are needed, and further study should be conducted to determine appropriate adjuvant chemotherapy for T1c TNBC patients.

Download Full-text

Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer

Journal of Clinical Medicine ◽

10.3390/jcm10040866 ◽

2021 ◽

Vol 10 (4) ◽

pp. 866

Author(s):

Agnė Bartnykaitė ◽

Aistė Savukaitytė ◽

Rasa Ugenskienė ◽

Monika Daukšaitė ◽

Erika Korobeinikova ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Estrogen Receptor Status ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Disease Assessment ◽

Her2 Status ◽

Nucleotide Polymorphisms ◽

Pcr Rflp ◽

Epidermal Growth

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.

Download Full-text

The Use of Atezolizumab + Nab-Paclitaxel for Women with PD- L1 Positive Advanced Triple-Negative Breast Cancer

International Journal of Research and Review ◽

10.52403/ijrr.20210707 ◽

2021 ◽

Vol 8 (7) ◽

pp. 36-43

Author(s):

Vahideh Beygi Rezagholi ◽

Sheby Elsa George ◽

Gouthami. U

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Triple Negative ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Survival Rates ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Tumor Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is an uncommon subtype of breast cancer that constitutes 15-20% of cases which has a poorer prognosis and lower survival rates (approximately 18 months or less with available treatments) compared to other types of breast cancer. As the name suggests, TNBC is immunohistologically marked by the lack of expression of factors namely estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2)/NEU gene. TNBC is characterized by high grades of Tumor-Infiltrating lymphocytes (TILs), programmed-death ligand 1 (PD-L1) expression, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as observed in other cancers too. Hence, metastatic TNBC (mTNBC) therapy focuses on the advancement of immune checkpoint inhibitors which block the above immune checkpoint proteins. The use of Atezolizumab (anti-PD-L1) in combination with nab-paclitaxel (chemotherapy agent) has been marked as a relevant advance in the treatment of metastatic, PD-L1-positive TNBC. It is better to consider advanced and approved diagnostic (VENTANA PD-L1 SP142 assay) in patients who get benefit from treatment with Atezolizumab plus nab-paclitaxel. Keywords: Triple Negative Breast Cancer (TNBC), Atezolizumab, Nab-paclitaxel, Chemotherapy.

Download Full-text

Radiotherapy and Adjuvant Trastuzumab in Operable Breast Cancer: Tolerability and Adverse Event Data From the NCCTG Phase III Trial N9831

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.9549 ◽

2009 ◽

Vol 27 (16) ◽

pp. 2638-2644 ◽

Cited By ~ 124

Author(s):

Michele Y. Halyard ◽

Thomas M. Pisansky ◽

Amylou C. Dueck ◽

Vera Suman ◽

Lori Pierce ◽

...

Keyword(s):

Breast Cancer ◽

Cumulative Incidence ◽

Early Stage ◽

Growth Factor Receptor ◽

Breast Conserving Surgery ◽

Phase Iii ◽

Cardiac Events ◽

Adjuvant Trastuzumab ◽

Significant Difference

Purpose To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy. Patients and Methods Patients with early-stage resected human epidermal growth factor receptor 2 (HER-2) –positive breast cancer (BC) were randomly assigned to doxorubicin (A) and cyclophosphamide (C), followed by weekly paclitaxel (T; AC-T-H or AC-TH-H). RT criteria (with or without nodal RT) were postlumpectomy breast or (optional) postmastectomy chest wall. RT of internal mammary nodes was prohibited. RT commenced within 5 weeks after T, concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms. Rates of cardiac events (CEs) with and without RT were compared within arms. Results No significant differences among arms were found in incidence of acute skin reaction, pneumonitis, dyspnea, cough, dysphagia, or neutropenia. A significant difference occurred in incidence of leukopenia, with higher rates for AC-T-H versus AC-T (odds ratio = 1.89; 95% CI, 1.25 to 2.88). At a median follow-up of 3.7 years (range, 0 to 6.5 years), RT with H did not increase relative frequency of CEs regardless of treatment side. The cumulative incidence of CEs with AC-T-H was 2.7% with or without RT. With AC-TH-H, the cumulative incidence was 1.7% v 5.9% with or without RT, respectively. Conclusion Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs. Further follow-up is required to assess late AEs.

Download Full-text

Association of Serum Leptin and C-Reactive Protein in Women with Breast Cancer

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.18.01.0368 ◽

2018 ◽

pp. 128-134

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Control Group ◽

Breast Cancer Patients ◽

C Reactive Protein ◽

Serum Leptin ◽

Reactive Protein ◽

Significant Difference

This study was conducted to evaluate the association of serum leptin and hs C-reactive protein with breast cancer. Two groups were included in the study. The first group included 45 newly diagnosed women with breast cancer. The second group included 42 women with benign breast lump as a control group. Blood samples (5 mL) were taken from the patient and the control groups and analyzed for serum leptin and hs C-reactive protein. Serum CA15-3 was also measured in breast cancer patients. The epidermal growth factor receptor 2 (HER2/neu), estrogen and progesterone receptors were determined in breast cancer patients by using immune-chemical method. Serum leptin was significantly higher (p ≤ 0.05) in breast cancer patients than that in the control group; however, no significant difference was noticed between the two groups for serum hs C-reactive protein. No significant difference was noticed between HER2/neu positive or negative in breast cancer patients for serum leptin or hs C-reactive protein. However, serum CA15-3 in HER2/neu positive patients was significantly higher (p ≤ 0.05) than that in HER2/neu negative patients. No significant difference was noticed between positive and negative estrogen breast cancer patients for serum leptin, hs C-reactive protein or CA15-3. In addition, no significant difference was noticed between positive and negative progesterone for serum leptin, hs C-reactive protein or CA15-3. A strong significant positive correlation was noticed between serum leptin and BMI in the control group; however, no significant correlation was noticed between serum leptin and BMI in the breast cancer patients. In conclusion, serum leptin may be used as a prognostic factor for breast cancer. Serum C-reactive protein in HER2/neu positive breast cancer patients is higher than in HER2/neu negative patients.

Download Full-text

Challenges and Perspectives on Breast Cancer Survivorship: The Journey Continues

Innovation in Aging ◽

10.1093/geroni/igaa057.317 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 96-96

Author(s):

Victoria Raveis ◽

Simona Kwon

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Cancer Survivor ◽

Breast Cancer Survivors ◽

Cancer Survival ◽

Survival Rates ◽

Extended Period ◽

Health Issues ◽

Age Related

Abstract Women have a 1-in-8 lifetime risk of breast cancer. Earlier diagnosis and treatment advances have improved 15- and 20-year survival rates. Increased survival can mean coping with the effects of cancer and its treatment over an extended period of time, while experiencing age-related changes in functioning and the emergence of other health issues. To explore breast cancer survivors’ perspectives on their issues and concerns across the life-course, focus groups were conducted with a culturally diverse sample (N=18) of survivors (72% white, 28% Black, 11% Hispanic). Participants were 44-82 years old. Most, 83% were 50 and older, 56% were 60 and older. The majority (83%) were diagnosed in their 40’s and 50’s. Two were diagnosed in their early 30’s and one at age 68. Participants reaffirmed the necessity, as a breast cancer survivor, of being a life-long health advocate on their own behalf, and the importance of being self-informed. As one woman commented: “Knowledge is power”. Survivors shared that their emergent health issues were complicated by their cancer history, and, that, as a cancer survivor, “I never stop worrying”. A widespread concern was not knowing if the health issues and co-morbidities they experienced (such as joint pain, neuropathy, tendinitis, heart disease), were age-related, a consequence of their cancer, or a late treatment effect. An overriding sentiment expressed was that clinicians have not recognized the importance of quality of life in cancer survival. As a survivor succinctly stated: “We are living longer, but we need to live long with quality of life.”

Download Full-text

Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Cancers ◽

10.3390/cancers13143427 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3427

Author(s):

Reyhaneh Farghadani ◽

Rakesh Naidu

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Mapk Pathway ◽

Growth Factor Receptor ◽

Progesterone Receptors ◽

Drug Candidate ◽

Molecular Signaling ◽

Her2 Positive ◽

Therapeutic Implications ◽

Epidermal Growth

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

Download Full-text

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽

10.1186/s12885-021-07855-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dechuang Jiao ◽

Jingyang Zhang ◽

Jiujun Zhu ◽

Xuhui Guo ◽

Yue Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cox Model ◽

Survival Rates ◽

Tumor Grade ◽

Population Based ◽

Rank Test ◽

Breast Cancers ◽

Significant Independent Predictor ◽

Cancer Specific Survival ◽

7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Download Full-text