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Radiation Therapy Considerations and Oncoplastic Breast Surgery


Introduction

The surgical treatment of breast cancer has undergone a paradigm shift and evolved from the Halsted radical mastectomy to the simple mastectomy and now includes breast conservation therapy (BCT). BCT is defined as local excision of the primary tumor (i.e., lumpectomy, quadrantectomy) or breast-conserving surgery (BCS) followed by radiation therapy (RT). BCT was ushered into standard of care by six large randomized prospective trials demonstrating equivalent survival rates with BCT compared with mastectomy in early disease. RT has been shown to be a critical component of the treatment regimen by reducing the recurrence rate by 50% and reducing breast cancer deaths by 16% after BCS. The goals of therapy with BCT are tumor eradication, prolonging survival, and maximizing quality of life with oncoplastic strategies.

Biological Basis of Radiation in Treatment of Breast Cancer

RT is defined as the delivery of ionizing energy to control malignancy while limiting damage to surrounding normal tissues. Two major methods of radiation delivery are available: (1) External Beam Radiation Therapy (EBRT) and (2) Brachytherapy. EBRT delivers high-energy photon or electron x-ray beams to tissue from outside the body. Brachytherapy delivers lower energy radiation within the patient’s body to treat the volume of tissue in the immediate vicinity.

Ionizing radiation as a therapeutic modality underwent rapid growth in the early part of the 20th century when Regaud demonstrated that certain internal reproductive cells may be targeted without causing major burns to the skin. The overarching goal is to optimize the “therapeutic ratio,” a risk benefit analysis of healthy versus cancerous tissue, when planning a radiotherapy regimen. The effect of radiation is known as the continuum , which describes the sequence of events that occur when ionizing energy is directed at a cell. Strong circumstantial evidence suggests cellular damage is a result of direct action of charged particles or free radical formation leading to DNA damage. At the later end of the continuum, reproductive integrity is lost when DNA is unrepairable or mis-rejoined, leading to cell death over hours to years. Tumor control is achieved when clonogenic cells are destroyed or otherwise unable to maintain growth.

Based on the theoretical radiobiological modeling of the dose response of normal tissue compared with cancer cells, conventional fractionation divides the total radiation into several smaller doses over a period of several days to impart less toxic side effects on late responding healthy cells. Cellular damage is regulated by the 4Rs of radiotherapy: r epair of sublethal damage between dose fractions, r eassortment of cells into more sensitive stages of the cell cycle, r eoxygenation of tumor cells for increased sensitivity, and r epopulation of the surviving fraction due to cell division.

Radiation in Breast Conservation Therapy and Invasive Ductal Carcinoma

BCT has become an alternative to mastectomy for most patients with early stage invasive ductal carcinoma. This is possible with modern multimodal patient selection and treatment. Indications for BCT are as follows ( Table 20.1 ) :

Table 20.1
Indications and Contraindications for Breast Conserving Therapy
Indications Contraindications
<5 cm tumor Inability to achieve negative margins ∗
Unifocal disease Prior chest irradiation ∗
Patient preference and compliance Poor aesthetic outcome ∗
Patients with comorbidities Inflammatory breast cancer ∗
Pregnancy
Collagen vascular disease
Prior breast augmentation

∗ Absolute contraindications

Early Stage Tumor/Tumor Size

The majority of trials demonstrating equivalent outcomes to mastectomy had upper size limit of 2–4 cm, whereas others permitted an upper limit of 5 cm. In tumors >5 cm or stage III, neoadjuvant chemotherapy should be considered before BCS. Older trials indicate local failure rate was significantly higher than those initially candidates for BCT (14.5% vs 6.9%). With improved patient selection and coordination among specialties, the locoregional control has been shown to be equal in those who do and do not receive neoadjuvant chemotherapy.

Unifocal Disease

Historically, multifocal (two or more tumors in the same quadrant) and multicentric (two or more tumors in the separate quadrant or 4–5 cm apart) disease has been considered a contraindication to BCT, with historical ipsilateral breast tumor recurrence (IBTR) rates of 20–40%. However, studies with carefully selected patients demonstrate IBTR rates at 10 years are comparable to mastectomy. These tumors tended to be multifocal, smaller (≤1 cm), without extensive ductal carcinoma in-situ (DCIS), and in older women. Clear margins are paramount, as positive margins and low-grade tumors were the strongest predictors of IBTR (see “Inability to Achieve Clear Margins”).

Patient Preference/Compliance

Patients presenting for BCT must be motivated to preserve the breast and be willing to adhere to the radiotherapy regimen to follow. Historically, no difference was seen in psychological adjustment between BCT and mastectomy, but improved body image and sexual function were seen in BCT cohorts. A recent study with the BreastQ questionnaire found breast conservation without reconstruction to be associated with lower physical well-being in the chest area, sexual well-being, and overall satisfaction compared with mastectomy and reconstruction, possibly due to resulting asymmetry and radiation effect ( Fig. 20.1 ). The addition of oncoplastic breast reconstruction results in high level of long-term satisfaction, improved quality of life, and self-esteem. Patients should be offered reconstruction when available and necessary (see “Inadequate Aesthetic Outcome”).

Fig. 20.1, Breast conservation therapy without plastic reconstruction demonstrating a contour abnormality on the left following radiation therapy. Breast excision involving greater than 10% of the breast volume without reconstruction results in significant patient distress and lower satisfaction. 34

Certain situations make BCT untenable due to the consequences associated with radiation. The conditions are as follows (Table 1):

Inability to Achieve Clear Margins

Margins, based on the recommendations of consensus statements, are defined as invasive cancer on inked margins, the presence of which results in a twofold to threefold increase in IBTR ( Table 20.2 ). This increase is not nullified by a boost of radiation, systemic therapy, or favorable biology. So long as negative margins are achieved, consensus statements agree that routinely obtaining wider margins does not necessarily result in decreased risk of IBTR. However, when close margins present in younger patients with extensive intraductal component (EIC), re-excision may be beneficial. Tumor distribution, shape, or proximity to the chest wall may preclude the ability to achieve negative margins. The likelihood of this occurrence is increased with multicentric disease. Persistent positive margin after reasonable surgical attempts may be an indication to convert to a mastectomy.

Table 20.2
Consensus Guidelines on the Use of Re-excision for Non-negative Margins after BCS after WBI for Early Invasive Breast Cancer
Adapted from Freedman G. Breast conserving therapy for invasive breast cancers. In: Bland K, Copeland E, Klimberg VS, Gradishar W, eds. The breast: comprehensive management of benign and malignant diseases . New York, NY: Elsevier; 2018:693–705.
Society Position
American College of Radiology (2015)

  • When margins are microscopically involved, re-excision should be pursued

  • Wider margins may be more important in young patients, estrogen receptor negative, or EIC

American Society of Breast Surgeons (2013)

  • Re-excision is not recommended for <2 mm margin after lumpectomy for invasive cancer, with or without DCIS. Re-excision is decided on by case, depending on number of close margins, location of margin, and radiation therapy

Society of Surgical Oncology/American Society for Radiation Oncology (2014)

  • When there is no ink on the tumor, wider margins do not lower risk of IBTR

  • No evidence of increased margin exists for patients ≤40 years old

  • Recurrence after positive margin is not mitigated by radiation boost, favorable biology, or systemic therapy

National Comprehensive Cancer Network (2015)

  • Negative margin is defined as no ink on tumor, as defined in the SSO/ASTRO guideline

  • It may be reasonable to treat select cases of focally positive margins with a radiation boost

American Society of Clinical Oncology (2014)

  • Endorses SSO/ASTRO guidelines

  • Emphasis on postlumpectomy mammography in cases with microcalcifications

Further differentiation can be made between extensively positive and focally positive margins, which is defined as tumor involvement in three or fewer low-power microscopic fields. The risk of 8-year IBTR among excised tumors with focally positive margins was only marginally increased and further mitigated by systemic therapy. These patients may still be candidates for BCT. Clinical consideration of re-excision and additional adjuvant systematic therapy is warranted if focal margin involvement is present.

Pregnancy

WBI should be avoided in pregnant women due to the risk of mutagenesis to the developing embryo. Application of accelerated partial breast irradiation (APBI) is still controversial and not routinely performed. Oftentimes, the pregnancy delays diagnosis of breast cancer, and patients present with larger tumors necessitating mastectomy. However, should the tumor characters allow BCT and the pregnancy allows for excision, radiation may be delayed until after delivery (see “Timing”).

Prior Chest Irradiation

Patients with a prior history of irradiation (breast cancer, Hodgkin’s lymphoma) are generally ineligible for BCT as total tolerable dose of the previously irradiated tissue will likely be exceeded. In such scenarios, the standard of care is mastectomy; however, case reports have been described with APBI in patients refusing mastectomy.

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