A case of elderly breast cancer achieving partial response by letrozole with stable disease to anastrozole as neoadjuvant endocrine therapy

An 85-year-old postmenopausal woman had multiple lesions in her right breast. Core needle biopsy showed solidtubular carcinoma with positive hormone receptor (ER+++, PgR-). She refused surgery and was then treated with anastrozole as neoadjuvant endocrine therapy. After seven months of the treatment, all lesions were increased or unchanged. The clinical response was judged as stable disease. Letrozole was chosen for the next therapy. After ten months, reductions in the tumors were noted, and the clinical response was judged a partial response. No side effects were observed. These two drugs are nonsteroidal aromatase inhibitors, and it is considered there is a cross-resistance between them. However, several studies have revealed letrozole was significantly more potent than anastrozole in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in vivo. This may be related to a difference in effect between the two drugs. It is suggested that letrozole as second-line endocrine therapy may be effective for postmenopausal breast cancer even after anastrozole failure.     

A case of advanced breast cancer successfully treated with primary endocrine therapy

We present a case of a premenopausal woman with advanced hormone-sensitive breast cancer who was successfully treated with primary endocrine therapy consisting of ovarian ablation followed by a combined endocrine regimen of the aromatase inhibitor fadrozole 2 mg daily and tamoxifen 20 mg daily. During the 5 months treatment period, PR evaluation of the loco-regional lesions was performed The patient then underwent mastectomy with axillary lymph node dissection followed by fadrozole and tamoxifen therapy. Throughout the treatment course, no adverse events were encountered and the patient has been enjoying a favorable quality of life. As shown by this case, primary endocrine therapy is a promising treatment option for hormonesensitive breast cancer. However, this modality should be continued to be regarded as experimental.     

Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy

Background:

Primary endocrine therapy (PET) with aromatase inhibitors (AIs) is an option in elderly patients unfit for or unwilling to undergo surgery. We studied the outcome of patients treated with letrozole as PET.

Methods:

Patients with early oestrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours were excluded. Reasons for offering PET, response, survival, cause of death, time to initial and best response, fracture incidence, and late failure rates were studied.

Results:

In all, 104 patients received PET due to frailty (n=48), comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up was 56 months (4–106). Eighty-five cancers responded to letrozole (stable disease (SD, n=19), reduction in size (PR, n=42), and complete response ((CR), n=24)). Median survival was 51 months (4–103), time to initial response (PR/CR) 4.5 months (2–24), and time to best response 8.5 months (3–50). Letrozole was stopped in 25 patients due to progressive disease (n=19), side effects (n=5), and patient choice (n=1). Only 12 of 49 deaths were from breast cancer.

Conclusion:

Letrozole is a reasonable alternative in elderly women with early ER/PR-positive invasive breast cancer who are unfit or unwilling to undergo standard therapy.     

A case of elderly locally-advanced breast cancer with skin ulcer responding to letrozole

We report an 84-year-old woman with an ulcerated tumor of her right breast. The histological examination showed invasive ductal carcinoma, ER (allred-score 8), PgR (allred-score 0), and HER2 (0). Computed tomography and bone scintigraphy showed no distant metastases. She was diagnosed with right locally advanced breast cancer (cT4bN2aM0, stageIIIB) and received hormone therapy with letrozole. One year after, the carcinoma was reduced in size and the skin ulcer had disappeared. Two years later, the carcinoma had grown back slightly, but the skin ulcer was still undetectable. Hormone therapy alone was considered useful for treatment of elderly locally advanced breast cancer patients.     

Advanced breast cancer in a patient achieving long-term SD after letrozole administration for liver metastasis developing during anastrozole therapy

We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.     

Surgical management of primary lung cancer in an elderly patient with preoperative empyema

A 74-year-old man with primary lung cancer developed preoperative empyema but was successfully managed surgically. The patient was given a diagnosis of c-T2N1M0, stage IIB, moderately differentiated squamous cell carcinoma, but before surgery pneumothorax and empyema developed, resulting from rupture of the carcinoma. Thoracic drainage, lavage and systemic administration of antibiotics improved his empyema. As there were no malignant cells in the drainage fluid, right middle-lower bilobectomy, empyemal cavity resection and lymph node dissection were performed. The bronchial stump was covered with an intercostal muscle flap. Thoracic drainage, lavage and systemic administration of antibiotics were performed for 6 days following the operation. The patient was discharged on the 27th postoperative day without any complications having developed. The pathological diagnosis of the tumor was p-T4N2(#7)M0, stage IIIB, br(-), ly(+), v(+), p3(pleura), pm1 and d0. He died of recurrence at home 18 months after the operation. We believe the following to be the minimum requirements for surgical management of such patients: (1) immediate thoracic cavity drainage and lavage with systemic antibiotic therapy, aiming at infection control before surgery; (2) prophylactic lavage of the thoracic cavity during and after surgery and (3) coverage of the bronchial stump with an adequate flap. Six reported cases of primary lung cancer with preoperative empyema are also discussed.     

A case of aromatase inhibitor-tolerant metastatic breast cancer revealing complete remission with high-dose toremifene therapy

A 78-year-old woman diagnosed with left breast cancer (T2N1M0, Stage II B) was given breast-conserving therapy with axillary dissection. Pathological findings of the tumor were: 2.5 cm in size, invasive ductal carcinoma, nuclear grade 3, positive lymphatic invasion and pN1a. ER and PgR were both positive, and HER2 was negative. Administration of anastrozole (1 mg/day) and UFT (300 mg/day) was performed as adjuvant therapy for 8 months. However, several subcutaneous nodules appeared in the left breast and left axilla, after 11 months. Cytology and histology of nodules indicated metastatic invasive ductal carcinoma. We began high-dose toremifene therapy (120 mg/day) (HD-TOR) for treatment of recurrence and complete remission (CR), and was obtained after 8 months in all recurrent lesions. In this study, we demonstrated a case of aromatase inhibitor-tolerant metastatic breast cancer revealing CR following high-dose toremifene therapy.     

A case of breast cancer with multiple bone metastases demonstrating complete remission with high-dose toremifene therapy

We report a 64-year-old woman who underwent mastectomy for stage II (T2N1M0) advanced breast cancer, in whom multiple spine metastases developed 18 months postoperatively. She received 6 cycles of CA (cyclophosphamide 500 mg/m2, ADM 50 mg/m2 3 wq) therapy and oral tamoxifen (20 mg/body) administration for adjuvant therapy. The multiple bone metastases of the spine were revealed by technetium bone scan. The level of serum tumor marker CA15-3 increased two times over the normal range 18 months after surgery. She also developed osteoporosis a few years later, so we selected high-dose toremifene administration (120 mg/body) as a second-line therapy. No adverse effects have occurred and bone metastases disappeared. Moreover, the tumor marker was also normalized 6 months after toremifene therapy started. It was shown that high-dose treatment of toremifene was useful for recurrent breast cancer with bone metastasis.     

Neoadjuvant endocrine therapy with anastrozole significantly downstaged an elderly breast cancer woman with locally-advanced breast cancer which became operable

A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.     

A case regarded as an occult breast cancer treated without mastectomy

A 51-year-old woman was admitted to our hospital with a chief complaint of left axillary tumors. No such tumors were detected in bilateral breasts by ultrasonic tomography, mammography, computed tomography, and magnetic resonance imaging. The core needle biopsy from the left axillary lymph node was examined, and the specimen revealed an occult breast cancer, because the microscopic findings resembled the breast cancer organization and immunochemistry revealed positivity of the estrogen receptor. The radical left axillary dissection was operated. Tamoxifen and FEC 100 6 cycles were selected as adjuvant treatment. At one year after operation, she has no recurrence. Carcinoma cells had portedly been recognized in the mammary gland with 82.7% of the cases who had undergone mastectomy for occult breast cancer. However, in many cases, the patient's consent for mastectomy was not obtained like as in this case, and the choice of treatment is often difficult. We considered that the case's accumulation was necessary to verify the possibility of the mastectomy omission to an occult breast cancer, presented the case report.     

A case of breast cancer with endocrine features

Cancer with endocrine features rarely occurs in the breast. We report a case of breast cancer with endocrine features in an 80-year-old woman. The tumors were treated by wide excision and a postoperative histopathologic diagnosis of carcinoma of the breast with endocrine features was made. Immunostaining was positive for chromogranin A, neuron-specific enolase and synaptophysin, but weakly argyrophilic. Widespread metastases occurred two months postoperatively, and the patient died of breast cancer 6 months after the first treatment     

Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer

Purpose  

Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain.     

An elderly patient with DCIS of the breast effectively treated with toremifene alone

An elderly patient with breast cancer received toremifene monotherapy for one year, and about 60% tumor remission rate was obtained. Since viability of the residual tumor was suspected on ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), lumpectomy was performed under local anesthesia. The histopathological diagnosis was ductal carcinoma in situ (DCIS). The patient did not undergo axillary lymph node dissection or systemic chemotherapy. The patient is alive without disease under postoperative radiotherapy and toremifene treatment. Toremifene monotherapy and/or preoperative adjuvant therapy with toremifene alone may be useful methods for elderly patients with breast cancer considering the patients' quality of life.     

Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool

Neoadjuvant endocrine therapy has been increasingly employed in clinical practice to improve surgical options for postmenopausal women with bulky hormone receptor-positive breast cancer. Recent studies indicate that tumour response in this setting may predict long-term outcome of patients on adjuvant endocrine therapy, which argues for its broader application in treating hormone receptor-positive disease. From the research perspective, neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of novel therapeutic agents.     

Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response

PURPOSE: We previously discovered an extracellular matrix (ECM) gene cluster associated with resistance to first-line tamoxifen therapy of patients with metastatic breast cancer. In this study, we determined whether the six individual ECM genes [collagen 1A1 (COL1A1), fibronectin 1 (FN1), lysyl oxidase (LOX), secreted protein acidic cysteine-rich (SPARC), tissue inhibitor of metalloproteinase 3 (TIMP3), and tenascin C (TNC)] were associated with treatment response, prognosis, or both. EXPERIMENTAL DESIGN: In 1,286 primary breast tumors, mRNA expression (quantitative real-time PCR) was related to clinicopathologic factors and disease outcome in univariate and multivariate analysis including traditional factors. RESULTS: TIMP3, FN1, LOX, and SPARC expression levels (continuous variables) were significantly associated with distant metastasis-free survival (MFS) in 680 lymph node-negative untreated patients (P<0.03). Using a calculated linear prognostic score, these patients were evenly divided into five prognostic groups with a significant difference in 10-year MFS of approximately 40% between the two extreme prognostic groups. Furthermore, high TNC expression as continuous variable was associated with (a) shorter MFS in 139 estrogen receptor-positive and lymph node-positive patients who received adjuvant tamoxifen therapy (hazard ratio, 1.53; P=0.001), and (b) no clinical benefit (odds ratio, 0.81; P=0.035) and shorter progression-free survival (hazard ratio, 1.19; P=0.002) in 240 patients in whom recurrence was treated with tamoxifen as first-line monotherapy. These results were also significant in multivariate analyses. CONCLUSION: FN1, LOX, SPARC, and TIMP3 expression levels are associated with the prognosis of patients with breast cancers, whereas TNC is associated with resistance to tamoxifen therapy. Further validation and functional studies are necessary to determine the use of these ECM genes in decisions regarding treatment and whether they can serve as targets for therapy.     

A case of left breast cancer resulting in complete response by primary systemic therapy

The patient was a 39-year-old woman, who noted a mass in her left breast. She was diagnosed with the left breast cancer (T4N2M0, stage IIIB) in our hospital. As primary systemic therapy, she received 4 cycles of FEC 100 every 21 days, and then 4 cycles of paclitaxel (180 mg/m(2)) every 21 days. Clinical CR was maintained, and a total mastectomy with axillary lymph node dissection was performed. The resected specimen showed no visible cancer cells in both the primary site and axillary lymph nodes. The effect of the chemotherapy was grade 3, pathological CR, and all lymph node metastases disappeared.