Locally advanced breast cancer encompasses a heterogeneous collection of breast neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. Patients with these tumors may be classified as stage IIB, III or IV breast cancer according to the American Joint Committee for Cancer Staging and End Results Reporting (TNM classification). Multidisciplinary therapy has become the treatment of choice for these patients. Primary or neoadjuvant chemotherapy followed by locoregional therapy, either surgery and/or radiotherapy, and postoperative systemic chemotherapy is now an accepted strategy. More than 70% of patients achieve an objective response (including pathological complete remission in 10%-25% of cases), and many patients experience downstaging through primary chemotherapy. Breast conservation is possible in 10%-40% of patients with locally advanced breast cancer; almost all patients initially are rendered disease-free, and long-term local control is achieved in over 70% of these patients. Primary chemotherapy is the initial choice of treatment for patients with locally advanced tumors, but it is unclear what the optimal sequence of subsequent therapies should be, whether one or two local treatment modalities are necessary, and whether any or different postoperative chemotherapy is needed. The efficacy of primary chemotherapy was demonstrated in several large prospective studies in patients with locally advanced breast cancer. The natural history of this disease was changed dramatically by the introduction of these combined modality therapies. Five-year disease-free survival rates of 35%-70% are commonly reported, and about 25%-40% of patients will survive beyond 10 years without recurrence. In summary, multidisciplinary therapy that includes primary chemotherapy provides appropriate local control and the possibility of breast conservation therapy; it increases surgical resectability and survival rates in patients with locally advanced breast cancer. The role of new innovative therapeutic strategies such as high-dose chemotherapy, with hematopoietic stem cell rescue, new cytotoxic agents and higher dose-intensity therapy is currently under evaluation in patients with locally advanced breast cancer.

https://theoncologist.onlinelibrary.wiley.com/doi/pdf/10.1634/theoncologist.1-1-8

Locally Advanced Breast Cancer.

Locally advanced breast cancer (LABC) accounts for 5% to 15% of new breast cancer cases in the United States and for 40% to 60% of new cases in nonindustrialized countries. The diagnosis of LABC includes tumors classified under TNM classification as stage IIB (T3N0), stage III (IIIA and IIIB), and regional stage IV breast cancer (ipsilateral supraclavicular lymph node [LN] metastases), according to the American Joint Committee for Cancer Staging. 1 Based on the TNM system, LABC tumors must be larger than 5 cm (T3) and/or involve the skin or chest wall (T4) with any node (N), stage. Tumors of any tumor (T) category with N2 (matted axillary LN) or N3 (internal mammary LN) are also considered LABC. Inflammatory breast cancer (IBC) is a particularly aggressive form of LABC that has highly metastatic features, and it is classified as stage IIIB in the TNM system. 42 Inflammatory breast cancer is a clinical-pathological entity characterized by the rapid development (usually within 3 months) of erythema and edema (also known as peau d'orange sign) and breast ridging (palpable striae in erythematous areas). In many cases no definite mass is found by physical examination or mammography. The typical mammographic finding is diffuse skin thickening. Microscopic examination of involved skin may show invasion of lymphatic vessels, although the typical pathologic findings are not needed to make the diagnosis of IBC. Patients with ipsilateral supraclavicular LN metastases (technically stage IV) and no evidence of distant metastases have a similar prognosis to patients with stage IIIB disease and are considered in the LABC category. 9 During the first half of the twentieth century, patients with LABC underwent extensive surgical procedures and aggressive radiotherapy. The radical mastectomy was developed by William Halsted at the Johns Hopkins University for LABC patients. In the 1940s, Haagensen and others 29 revisited the surgical indications for patients with LABC. These authors recognized that patients with extensive skin involvement or fixation to the chest wall (currently classified as T4 lesions) had a high rate of metastases and mortality when treated with surgery alone. For this reason (and not because of technical issues), patients with T4, N3, or regional M1 (stage IIIB/IV) were considered inoperable. Using surgery or radiation therapy (RT) as single-therapy modalities resulted in local control for most patients with LABC. However, more than 80% of patients died of metastatic disease within 5 years of follow-up. The prognosis was particularly poor for patients with IBC treated with local regional therapy only. 36

pdf/locally-advanced-breast-cancer-4hp7y32059.pdf

Locally advanced breast cancer

Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children.

A comparative theoretical study on the interaction of pure and carbon atom substituted boron nitride fullerenes with ifosfamide drug

Myelosuppression is one of the serious side effects of anticancer chemotherapeutic drugs that deteriorate the bodily functions of patients, thereby affecting the quality of life considerably. Prevention of myelosuppression in anticancer chemotherapy is an important research topic. A stabilized chemotherapy-induced myelosuppression animal model is necessary in experimental research. This study aimed to establish an optimized animal model of chemotherapy-induced bone marrow suppression. After C57BL/6 mice were treated with intermediate- and high-dose (25/50 mg/kg) cyclophosphamide (CTX) for 10 days, the body-weight, changes in thymus and spleen, number of white blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs) and changes in bone marrow in the mice were systematically evaluated at the next 2, 7 and 14 days. Our results demonstrated that CTX treatments could significantly decrease the body-weight of mice, as well as the ratios of the weights of thymus and spleen to body-weight. The physiological structures of thymus and spleen were destroyed by CTX treatments. The number of WBCs and RBCs significantly declined after CTX treatments; however, the number of PLTs increased. Moreover, the expression of Sca1 in bone marrow cells decreased on Day 2 but increased on Day 14. The expression of CD34 decreased in bone marrow cells after CTX treatments. In conclusion, mice models, with high-dose CTX treatments for 10 days, can be an optimized animal model for chemotherapy-induced bone marrow suppression.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bcpt.12600

Optimized Animal Model of Cyclophosphamide-induced Bone Marrow Suppression.

Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaign

/pdf/ifosfamide-cisplatin-and-etoposide-combination-in-locally-2cwnlnm844.pdf

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study.

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Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study.