Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER-2+ Breast Cancer

505 Background: Disseminated tumor cells (DTC) in the bone marrow (BM) are related to poor prognosis of primary breast cancer (PBC). Cancer-initiating stem cells (CSC) have been detected in BM of PBC patients. Downregulation of the Notch pathway leads to murine mammary stem cell expansion and its expression is an early event in breast cancer. We enumerated CSC in BM mononuclear cells (BMC) and assessed the expression of Notch-1, ER, and HER-2 to study the differences between untreated patients and those treated with neoadjuvant chemotherapy. Methods: BM was collected from 90 PBC patients at time of surgery to assess DTC (CD326+CD45-) and CSC (CD326+CD45-CD44+CD24-) by FACS analysis. BM samples were also interrogated for the presence of CSC with ALDH activity using the Aldefluor® detection kit. RNA extracted from 61 BMC was analyzed for Notch-1, ER, and HER-2 transcripts by RT-PCR; the level of each transcript was normalized to that of the housekeeping gene, GAPDH. Results: The median age of patients is 51 years old (range, 27–77 years). A total of 29 patients (32%) received neoadjuvant chemotherapy, including 8 patients with anti-HER-2 targeted therapy. BMC of neoadjuvant-treated patients had a significantly higher median percentage of CSC in BMC (P= 0.046) and a significantly higher proportion of CSC cells within the Aldefluor+ population (P= 0.013) than those of untreated patients. Median level of Notch-1 transcripts in BMC was lower in neoadjuvant-treated patients compared with that of untreated patients (P= 0.07). There was an inverse correlation between the level of Notch-1 transcripts and the percentage of CSC in BMC of untreated (Spearman's rho= -0.519, P < 0.001), but not in neoadjuvant treated (Spearman's rho= -0.483, P= 0.058) patients. Conclusions: Neoadjuvant chemotherapy is associated with expansion of CSC in the BMC of patients with PBC. Untreated patients with higher level of Notch-1 transcripts in the BMC tend to have lower percentages of CSC and suggest that Notch signaling may be crucial for differentiation of CSC. The prognostic value of this finding is under investigation and gene expression profile of CSC may provide indications for novel neoadjuvant therapies. No significant financial relationships to disclose.

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Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11516 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11516-e11516

Author(s):

A. Guerrero-Zotano ◽

J. Gavila ◽

M. A. Climent ◽

M. J. Juan ◽

V. Guillem ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Breast Cancer Subtypes ◽

Nuclear Staining ◽

Luminal A ◽

Long Term Outcome ◽

Cancer Subtypes ◽

Luminal B ◽

Her 2

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.

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A retrospective study of inflammatory breast cancer patients from seven hospitals in the United Kingdom.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e11062 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e11062-e11062

Author(s):

Saeed Rafii ◽

Christopher John Poole ◽

Adele Francis ◽

Shalini Chaudhri ◽

Daniel Rea

Keyword(s):

Breast Cancer ◽

United Kingdom ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Inflammatory Breast Cancer ◽

Triple Negative ◽

Breast Cancer Patients ◽

The United Kingdom ◽

Her 2 ◽

Clinical Records

e11062 Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterised by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d’orange. It is estimated that between 1-4 % of all newly diagnosed breast cancer patients in the United Kingdom have IBC. Methods: We retrospectively identified 51 patients who were treated for IBC at 7 hospitals in the West midlands area of the United Kingdom between 1997 and 2011. Data including patients’ demographics, clinical, radiological and histopathological characteristics were collected from electronic clinical records. The test for HER-2 over-expression was not carried out routinely before 2002, therefore HER-2 status of such patients were assessed retrospectively on the archived tissues. A cox regression analysis was used for statistical assessment of survival and prognostic factors. Results: Median age at diagnosis was 55 years (range 34-83 yrs). Median overall (OS) and progression free survival (PFS) were 32 months (range 7-97 months) and 27 months (range 2-53 months) respectively. The 3–year survival rate for the entire cohort was 32%. Majority of patients were ER and HER-2 positive (49% and 52% respectively). The rate of complete pathological response (pCR) after neoadjuvant chemotherapy was 14%. All cases who had achieved pCR were HER-2 positive who had received anti HER-2 treatment during the neoadjuvant chemotherapy. The OS for the HER-2 positive patients with pCR was not statistically different from the whole cohort (49 vs 32 months, p=0.09) or from the patients with residual disease (49 vs 26 months, p=0.13). Although the triple negative IBC patients consisted 20% of the cohort, no patients in this group had achieved pCR. The OS and PFS for the triple negative patients were 20 and 14 months respectively. Although the rate of pCR was higher in patients treated with taxane compared to those treated with anthracycline containing chemotherapy (35% vs 7%), there was no significant difference in OS between either of these regimens (29 vs 27 months). Conclusions: HER-2 positive IBC patients had higher rate of achieving pCR after neo-adjuvant anti HER-2 therapy. However higher rate of pCR did not improve the OS.

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