Markiewicz D A, Schultz D J, Haas J A, Harris E E, Fox K R, Glick J H, Solin L J
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Int J Radiat Oncol Biol Phys. 1996 Jul 1;35(4):661-8. doi: 10.1016/0360-3016(96)00171-x.
Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy.
The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy +/- hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate (CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up.
The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome (p = 0.78). The incidence of Grade 4 or 5 arm edema (> or = 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy (p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p > or = 0.52). Patients treated sequentially had a 10% incidence of Grade 4 or 5 arm edema vs. 7% in the patients treated concurrently (p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF (p = 0.73). The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p > or = 0.06).
Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.
化疗在淋巴结阴性和阳性乳腺癌患者的治疗中发挥着越来越重要的作用，但化疗与放疗的最佳顺序尚未明确确立。本研究的目的是评估化疗和激素治疗的顺序及类型与放疗联合应用时，对接受保乳治疗的Ⅰ期和Ⅱ期乳腺癌患者美容效果和并发症发生率的相互影响。
回顾了1977年至1991年间1053例接受保乳手术、腋窝清扫和放疗的Ⅰ期和Ⅱ期乳腺癌患者的病历。治疗后的中位随访时间为6.7年。214例患者仅接受化疗，141例患者仅接受激素治疗，86例患者两者均接受，612例患者未接受辅助治疗。接受化疗±激素治疗的患者根据化疗顺序分组：（a）同步组=放疗时同步化疗，随后再进行化疗；（b）序贯组=放疗后化疗或化疗后放疗；（c）夹心组=化疗后同步进行化疗和放疗，随后再进行化疗。与淋巴结阴性患者相比，淋巴结阳性患者更常接受化疗（77%对9%，p<0.0001）和/或激素治疗（40%对14%，p<0.0001）。在接受化疗的患者中，大多数（243例患者）在放疗期间接受两个周期的环磷酰胺和5-氟尿嘧啶（5-FU）同步化疗，随后用环磷酰胺、5-氟尿嘧啶和甲氨蝶呤（CMF）或多柔比星（CAF）进行六个周期的化疗。为了分析美容效果，纳入的患者为无复发且至少随访3年。
与未接受化疗相比，化疗的使用对美容效果有不良影响，在3年时具有临界显著性（美容效果优良率分别为92%对96%，p=0.057）；然而，5年时美容效果无差异（分别为91%对93%，p=0.67）。序贯治疗的患者与同步治疗的患者美容效果无显著差异（3年时分别为87%对93%，p=0.33），接受CMF与CAF治疗的患者之间也无差异（3年时分别为92%对93%，p=0.89）。激素治疗未影响美容效果（p=0.78）。未接受化疗时4级或5级手臂水肿（手臂周长差异≥2cm）的发生率为2%，接受化疗时为8%（p=0.00002）。然而，手臂水肿的发生率不受化疗顺序或类型的影响（所有p≥0.52）。序贯治疗的患者4级或5级手臂水肿的发生率为10%，同步治疗的患者为7%（p=0.52）。接受CMF治疗的患者发生率为7%，接受CAF治疗的患者为9%（p=0.73）。临床肺炎和肋骨骨折的发生率不受化疗使用、化疗顺序或激素治疗的影响（所有p≥0.06）。
与接受其他化疗顺序的患者相比，在对Ⅰ期和Ⅱ期乳腺癌患者进行保乳治疗时，化疗可与放疗同步进行，而不会严重影响美容效果或并发症发生率。激素治疗不影响美容效果或并发症。环磷酰胺和5-FU与放疗同步进行，随后再进行更多化疗的化疗方案是需要化疗的患者保乳治疗的一个合理选择。
