Adjuvant Radiation Therapy After Breast Conserving Surgery

    • Survival: Between 1961 and 1989, multiple international randomized clinical trials were performed to directly compare breast-conserving therapy (BCT) with mastectomy
    • These trials consistently demonstrated similar overall and breast disease-specific survival (DSS) between the two approaches
    • Since then, BCT has been considered at least equivalent to mastectomy in survival outcomes
  • Since 2013, a growing number of studies, both in the United States and internationally:
    • Have associated BCT with better survival than mastectomy, regardless of age, stage, tumor characteristics, and cancer phenotypes
    • As examples:
      • One cohort study of over 110,000 Californian women with stage I or II breast cancer:
        • Associated BCT with better overall survival (OS) than mastectomy without radiation (adjusted hazard ratio [HR] 0.81, 95% CI 0.80-0.83)
        • The DSS benefit was more pronounced among women age ≥ 50 with hormone receptor-positive disease (HR 0.86, 95% CI 0.82-0.91):
          • But was seen in all subgroups analyzed regardless of age, hormone receptor status, and cancer phenotypes
      • In a population-based study from the Netherlands that included over 170,000 patients, BCT conferred a survival advantage over mastectomy (HR 0.87, 95% CI 0.81-0.93) following correction for stage, age, and adjuvant therapies
    • However, all of these were observational studies, which could be confounded by selection bias
    • Thus, BCT is still considered “at least” equivalent:
      • Rather than superior to, mastectomy in survival outcomes
    • Both approaches are acceptable options that should be selected based upon multidisciplinary clinician input and patient preference
  • The biologic plausibility of a more limited procedure (BCS) being superior to a more radical surgery (mastectomy):
    • Can potentially be explained by the impact of adjuvant radiotherapy (RT) and the fact that mastectomy may not remove all breast tissue (thus leaving behind microscopic cancer foci)
    • Indeed, we know that the success of BCT is contingent upon moderate-dose RT in eliminating subclinical foci of disease in the ipsilateral breast
    • Adjuvant RT has been shown to substantially reduce the risk of in-breast recurrences
    • Additionally, the isolated axillary recurrence rate after BCT:
      • Has been shown to be lower than that after mastectomy without radiation:
        • 1.1% versus 3.5% in a prospective nonrandomized study with 13 year follow-up
      • In that study, both overall survival (79.5% versus 64.3%) and disease-free survival (90.5% versus 84%) were better after BCT than after mastectomy:
        • Although the ipsilateral breast or chest wall recurrence-free survival rates were not statistically different (90.5% BCT versus 95% mastectomy; p = 0.428)
      • Thus, the survival benefit of BCT should at least be partially attributed to the protective effect of radiation
      • The tangential radiation fields originating from whole breast irradiation may help reduce recurrence by controlling minimal residual disease in the lower axilla
  • Local recurrence:
    • Local control is important to overall survival:
      • Because local failure is a risk factor for distant metastasis
    • Rough estimates indicate that:
      • One patient may die from breast cancer for every four local recurrences
    • A higher locoregional recurrence rate for BCT:
      • Was reported in some of the early trials comparing BCT with mastectomy
    • In randomized studies using variable surgical and radiation techniques:
      • Long-term recurrence rates in the treated breast following BCT range from:
        • 5% to 22%, compared with 4% to 14% with mastectomy
        • In those days, the risk of local recurrence after BCT was estimated to be around 1% per year, or 10% at 10 years:
          • However, the higher local recurrence rate did not appear to negatively impact survival
        • Since then, better imaging, more attention to margins, and more effective and longer durations of systemic therapy have reduced local recurrence rate after BCT to just:
          • 2% at 10 years:
            • Thus, the local recurrence rate after contemporary treatment with BCT is no longer considered higher than that after mastectomy
    • The local recurrence rate following BCT increases with:
      • Young age
      • Positive surgical margins
      • Node positivity
      • Estrogen receptor negativity
      • Absence of radiation therapy
    • It is important to realize that these factors are not contraindications to BCT:
      • But their presence may influence the choice of treatment
  • Cosmetic outcome:
    • In addition to local recurrence, another major goal of BCT is the preservation of a cosmetically acceptable breast
    • With modern treatment techniques, an acceptable cosmetic outcome can be achieved in almost all patients without compromising local tumor control
    • Many surgical factors will play a role in the ultimate cosmetic appearance of the breast:
      • These include the size and placement of the incision, management of the lumpectomy cavity, and the extent of axillary dissection if necessary
      • The surgeon has control over several of these issues, and careful attention to detail will improve the aesthetic results
      • The amount of resected breast tissue is the major determinant of appearance following BCS
      • Oncoplastic surgical techniques allow resection of a breast cancer with wide surgical margins while preserving the shape and appearance of the breast:
        • Patients with either:
          • A large tumor relative to their breast size or a central tumor are candidates for oncoplastic resections
        • Long-term outcomes of oncoplastic surgery are comparable or superior to those of standard breast conservation surgery
    • Adjuvant radiotherapy can also influence cosmetic outcomes by:
      • Causing skin fibrosis:
        • The primary approach to prevention of radiation-induced fibrosis is through the use of appropriate radiation therapy doses and techniques that minimize the radiation exposure for normal tissue
        • For patients with established radiation-induced fibrosis, treatment is primarily symptomatic and includes:
          • A combination of pentoxifylline and tocopherol (vitamin E)
    • Although treatment-related changes in the breast stabilize at approximately three years:
      • Other factors that affect the untreated breast, such as change in size because of weight gain or the normal ptosis seen with aging:
        • Continue to affect breast symmetry
    • Such less-than-ideal cosmetic results can be remedied by reconstruction of the ipsilateral or contralateral breast

#Arrangoiz #BreastCancer #BreastSurgeon #CancrerSurgeon #Miami #SurgicalOncologist #CASO #CenterforAdvancedSurgicalOncology

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