Special technical details: wide local excision

The aim of wide local excision is to remove all invasive and any ductal carcinoma in situ with a margin of normal surrounding breast tissue. Controversy has surrounded which incisions give the best cosmetic results. The predominant orientation of collagen fibres in the skin was described by Langer²⁵ and these skin crease lines around the breast are essentially circular (Fig. 4.1). Subsequent work by Kraissl²⁶ demonstrated that the lines of maximum resting skin tension run in a more transverse orientation across the breast (Fig. 4.1). In general, scars that are parallel both to the lines of maximum resting skin tension and to the orientation of collagen fibres are quickest to heal and produce the best cosmetic outcomes, with the lowest rates of scar hypertrophy and keloid formation.

A knowledge of Langer’s lines and Kraissl’s lines thus allows a surgeon to make incisions that enhance the cosmetic outcome of breast-conserving surgery. It has been tradition to place an incision to excise a cancer directly over the lesion, but this can result in an unsightly scar, particularly if the cancer is high and medial. In such instances placing the scar some distance below in the skin crease lines and tunnelling up to the lesion produces a better cosmetic result. Cancers close to the nipple and even those some distance away in the upper half of the breast can be excised through circumareolar incisions. A cancer low in the breast close to the inframammary fold can similarly be excised through an incision placed in the fold. A cancer in the upper outer quadrant can be excised easily through an axillary incision. Excising skin directly overlying a cancer is only necessary if the skin is involved. It is not necessary to remove dimpled or tethered skin. The cosmetic result after breast-conserving surgery is influenced by the amount of skin excised, with poor results being obtained in those patients who have most skin removed. In patients with direct skin involvement, the aim should be to minimise the skin excised and to remove only enough skin to get microscopically clear margins.

Limiting the length of incision is also important, as longer incisions produce significantly poorer cosmetic outcomes. A knowledge of the depth of the cancer within the breast provided by preoperative or intraoperative breast ultrasound can be valuable when planning the extent of excision. For instance, if a cancer is 2 cm deep within the breast, then at least 1 cm of fat and subcutaneous tissue can be left on the skin flaps; leaving this tissue improves the cosmetic outcome. Whatever incision is used, it is important to have discussed the position of all scars with the patient prior to surgery.

Having made the skin incision, the skin and subcutaneous fat are dissected off the breast tissue. Care should be taken when elevating skin not to remove subcutaneous fat unnecessarily as thin skin flaps give a poor postoperative cosmetic result. Where the cancer is close to the skin, hydrodissection infiltrating 1 in 400 000 adrenaline in saline can help to separate the skin and subcutaneous fat from the breast tissue and breast fat, and facilitates skin elevation over the cancer. Skin flaps beyond the edge of the cancer for at least 1–2 cm are mobilised. This allows the fingers of the non-dominant hand to be placed over the palpable cancer. The breast tissue is then divided beyond the fingertips. The line of incision through the breast should be approximately 1 cm beyond the limit of the palpable mass. Having incised through the breast tissue, dissection continues under the cancer. In the majority of patients it is necessary to divide the whole thickness of breast tissue down to the pectoral fascia, to ensure that there is an adequate margin of tissue removed deep to the cancer. If the lesion is superficial, and there is a significant amount of breast tissue deep to the cancer, it may not be necessary to remove full thickness of breast tissue. Likewise if the lesion is deep, more tissue can be left superficially on the skin flaps. Having reached the deep margin, which is usually the pectoral fascia, the breast tissue and cancer are lifted from this fascia. It is not necessary to excise pectoral fascia unless it is tethered to the tumour or the tumour is involving it. If a carcinoma is infiltrating one of the chest wall muscles, then a portion of the affected muscle should be excised beneath the tumour, the aim being to remove sufficient muscle to get beyond the limits of the cancer. Having dissected under the cancer, the cancer and surrounding tissue are grasped between the finger and thumb of the non-dominant hand and excision of the cancer at the other margins is completed. The specimen should be orientated immediately following excision with Liga-clips, sutures or metal markers, prior to specimen radiography and submission to the pathologist.²⁷ Metal markers or Liga-clips are preferred because they can be seen on specimen radiography. Routine X-ray of orientated specimens is recommended because it has been shown to help the surgeon confirm the target lesion has been excised and allows assessment of completeness of excision at the radial margins.²⁷ If the specimen radiograph shows the cancer or any associated microcalcification is close to a particular margin, then further tissue can and should be removed from the margin of concern, before being orientated and sent to pathology.

A number of studies have evaluated the use of cavity shavings and bed biopsies, but few have compared these with standard assessment of margins. A minority of surgeons continue to take cavity shavings and bed biopsies routinely. Neither has been shown to be reliable indicators of local recurrence. A major concern of taking cavity shavings routinely is that significant amounts of extra breast tissue can be removed, particularly if the whole cavity is shaved; this unfortunately can adversely affect cosmetic outcome. Most importantly, however, centres who do not use these techniques report excellent local control rates, which have continued to fall over time.^28,29 Wide excision with standard examination of margins thus provides sufficient information on margin status for clinical use. Bed biopsies or cavity shavings are only of value and warranted where there is concern at operation that one particular margin is involved.

New devices that use ultrasound or rely on the electrical properties of the tissue are in trials and are being used to assess whether they can detect margin involvement and facilitate increased rates of complete excision at the first operation.

Having excised the cancer from the breast, suturing the defect in the breast without mobilisation of the breast tissue usually results in distortion of the breast contour. Defects in the breast are best closed by mobilising surrounding breast tissue from the overlying skin and subcutaneous tissue and in some patients mobilisation from the underlying chest wall is required. Large defects (> 10% breast volume) that are left open fill with seroma, which often absorbs later, following which scar tissue develops and contracts and can result in an ugly distorted breast. Following large-volume excisions, after mobilisation it is usually possible to close the defect in the breast tissue by a series of interrupted absorbable sutures. Given the success of lipofilling or lipomodelling for improving some patients with poor cosmetic outcomes following breast-conserving surgery and radiotherapy, a number of surgeons are exploring whether immediate lipofilling after wide local excision can improve outcomes, particularly for women with small breasts. Very large defects require oncoplastic breast reshaping (see Chapter 6) or a latissimus dorsi miniflap.^12,13 Drains are not necessary after wide local excision and should not be used routinely. They do not protect against haematoma formation and increase infection rates. Breast skin wounds should be closed in layers with absorbable sutures, finishing with a subcuticular suture.

Complications of wide excision include haematoma, infection, incomplete excision, seroma and poor cosmetic results. Haematoma requiring evacuation is uncommon but occurs in approximately 2% of patients. Infection requiring treatment affects 5–10% and is more common when combined with an axillary dissection. Incomplete excision rates should be in the range 10–25%. The most common problem following surgery by wide local excision is a poor cosmetic result. Factors influencing cosmetic outcome and methods of avoiding this are considered in detail below.

Excising impalpable cancers

Impalpable lesions can be localised prior to surgery using one of a number of different techniques, including skin marking, injection of blue dye, carbon or radioisotope, insertion of a hooked wire, or intraoperative ultrasound. Although excising an impalpable cancer is easier if the skin incision is made directly over the cancer, remote incisions produce the best cosmetic results. Most impalpable small cancers should thus be approached through a cosmetically placed incision. The location of the lesion can be determined in a number of ways: (i) the surgeon can calculate the position of the breast lesion from the mammogram taken after wire insertion; (ii) the radiologist or the surgeon can mark the skin overlying the lesion using ultrasound; or (iii) if radioactivity has been injected to localise the cancer, the surgeon can use a gamma probe to localise the area of maximum radioactivity. After making an appropriately sized and cosmetically placed skin incision, this is deepened. If a wire is in place, then dissection continues towards the wire in the plane between the breast and subcutaneous fat so that the wire can be located some distance before it enters the lesion. For instance, if a mammographic abnormality has been localised in the craniocaudal position, then it helps to identify the wire superiorally before it enters the cancer. Wires that are marked with beads or that change in diameter, or have a guide that can be placed over the wire, help the surgeon to determine exactly how far along the wire the lesion is situated. Ideally the hook of the wire should be 1 cm through the lesion rather than within its centre. The direction of the wire on the preoperative mammogram is not always a reliable guide to the course of the wire through the breast. Once the wire is in place standard mammographic views are not always possible and thus a lesion that is apparently lateral to the entry point of the wire may not be lateral on the check craniocaudal film once the compression from the breast has been released. The aim is to remove the mammographic lesion with a 1-cm clear radiological margin and in most women to excise tissue up to subcutaneous fat and down to pectoral fascia.

As for palpable lesions, all specimens should be orientated with Liga-clips or metal markers, or secured to an orientated grid so that an orientated specimen radiography can be performed. Radiography is best performed in an X-ray machine designed specifically to X-ray specimens, such as a Bioptics® machine. There have been conflicting reports about whether compressing the specimen affects the incidence of subsequent positive margins as reported by the pathologist. Orientated specimen radiography improves the rate of complete excision of impalpable cancers.²⁷ Cooperation between surgeon and pathologist is required so that the area of concern can be identified and assessed by the pathologist to ensure adequacy of excision.

The majority of wide excisions of palpable and impalpable cancers are performed under general anaesthesia, but it is possible to perform these procedures under local anaesthesia.

Patient-related factors

In contrast, local recurrence is much less of a problem in older patients (> 65 years).

Recurrence is less frequent in women with large breasts but whether this relates to the larger excisions that can be performed in these patients or to alterations in steroid metabolism (fat is known to be an important site of conversion of androgens to oestrogens) is uncertain.³⁶ A family history of breast cancer, particularly carriage of a mutation in one of the breast cancer genes, predisposes a patient to an increased rate of second primary cancers in both the treated and contralateral breast unless these women undergo a prophylactic oophorectomy, when local recurrence rates fall to levels similar to those of the general population.^37,38

Tumour-related factors

Tumour location, tumour size, the presence of skin or nipple retraction, and the presence or absence of axillary node involvement have not been shown consistently to predict for local recurrence after breast-conserving surgery.39–42 The hormone receptor status of a breast cancer does not seem to exert any influence on local control rates.^{31–35,39–42} In-breast tumour recurrence has been reported to be more common in human epidermal growth factor receptor (HER2)-positive cancers.

Treatment-related factors

Controversy has surrounded how much extra tissue around a cancer needs to be removed and what constitutes an involved or positive margin. Some studies have defined a positive or involved margin as disease at the margin, others consider disease within 1 mm or even disease within 2 mm of the margins as involved. Conversely, negative margins or uninvolved margins have been variably defined as no tumour at the margin, or tumour within 1, 2, 5 and 10 mm of the margin. Whatever definition has been used, almost all studies have reported an increased rate of local recurrence in patients with positive, non-negative or involved margins. When comparing patients with involved margins to those with uninvolved or negative margins, the relative risk of local recurrence varies between 1.4- and 9-fold.^{28,29,31–35,39–42,45–47,49–54} This is despite, in almost half of these series, patients with involved or close margins having received higher doses of radiotherapy than patients with clear margins. In the few studies which found that margins are not important predictors of local recurrence, the dose of radiotherapy delivered to the tumour bed ranged from 65 to 72 cGy, i.e. a dose range that is effective without surgery.^51–54 In one study, patients with involved margins who underwent re-excision to achieve a negative margin had a zero local recurrence rate; this compares with a 22% local recurrence rate in those patients who had re-excision but still had non-negative margins (P = 0.001).⁵⁰ Surveys in the UK and USA have demonstrated that approximately 50% of surgeons aim for a margin of more than 2 mm, whereas 50% of surgeons are happy with a margin of 2 mm or less.⁵⁵ There is thus no consensus about what constitutes an adequate margin of excision for breast-conserving surgery. A systematic review of margins and local recurrence was conducted by Singletary, who reported that some of the lowest rates of local recurrence were in centres that had used narrow margins of excision (1 or 2 mm).²⁸ A recent large comprehensive meta-analysis of margins has confirmed that wider margins do not reduce local recurrence.²⁹ Wider margins remove more tissue and so impact on cosmetic outcomes. The meta-analysis confirmed an increased rate of local recurrence for both involved and close (< 1 mm) margins.²⁹ Compared with no ink on cancer cells a 1-mm margin was associated with a significantly lower rate of local recurrence. Recent data from Edinburgh show there is no need to re-excise if anterior or posterior margins are < 1 mm, providing full thickness of breast tissue has been excised and boost radiotherapy given. Unpublished data from Edinburgh show similar local recurrence rates whether the distance to the nearest margin was in the range 1–5 mm or 5–10 mm, confirming the results from the meta-analysis that narrow 1-mm margins are sufficient.

A recent large series of patients treated by breast-conserving surgery with a ≥ 1 mm margin reported rates of local recurrence of < 0.5% per year (Fig. 4.2).⁵⁶ The majority of these so-called recurrences were in fact second primaries. In conclusion, a 1- or 2-mm margin is adequate and produces acceptable rates of long-term control. Any centre excising margins wider than 1 or 2 mm on breast-conserving excisions should consider their protocols.

Studies have looked at the presence of lobular carcinoma in situ⁵⁷ and atypical ductal hyperplasia⁵⁸ at the margins of excision. Neither of these features significantly increases local recurrence rates and so there is no need for re-excision if the pathologist reports these features alone at any of the margins of excision.

Age interacts with margins. Involved margins have their greatest impact on local recurrence in younger rather than in older women.⁵³

There is a direct interaction between EIC and margins (Table 4.2). Patients with EIC and positive margins who proceeded to radiotherapy without re-excision had a 37% local recurrence rate in a series from Boston⁴⁸ and a 21% recurrence rate in a Stanford series.⁵⁰ In contrast, patients with EIC and negative margins, on primary or re-excision, had a zero local recurrence rate. These two studies demonstrate that patients with EIC do not have an increased rate of local recurrence providing the margins of excision are clear of invasive and in situ cancer.

Patients undergoing re-excision for close or involved margins have only a 30% incidence of residual cancer in re-excised tissue.⁵⁹ More than two foci of microscopic margin involvement in the original wide excision appears to be associated with a greater incidence of residual cancer (65%) compared with fewer than two foci, which had a much lower rate of residual cancer. If there was no residual disease at re-excision then there was a 4% local failure rate at 4.7 years compared with a 13% failure rate in patients who had residual disease at re-excision. Patients younger than age 50 in this study were also more likely to have disease in the re-excision specimen. The conclusion was that the majority of patients who undergo re-excision do not benefit from this procedure. Patients with lucent breasts and a well-defined lesion appear particularly unlikely to benefit from re-excision, if margins are close or focally positive, whereas younger women with dense breasts are much more likely to benefit from further surgery, as many of these women will have residual disease in the re-excision specimen.⁵⁹ Further studies in this area are required. If it were possible to identify a group of women who do not benefit from re-excision, this would have great clinical utility.

Adjuvant systemic therapy

Aromatase inhibitors, tamoxifen and chemotherapy, in the presence of radiotherapy, reduce local recurrence rates after breast-conserving surgery.^60,61 In the absence of radiotherapy, aromatase inhibitors, tamoxifen or chemotherapy alone do not produce satisfactory rates of local control apart from in low-grade, node-negative cancers.⁶² The interval between surgery and radiotherapy may be important and there are suggestions that the rates of local recurrence increase if radiotherapy is delayed. The sequencing of radiotherapy and chemotherapy is the subject of ongoing trials but it appears that giving both synchronously rather than sequentially improves local recurrence.

Patient factors

There is conflicting evidence about whether age influences cosmetic outcome, with some studies claiming that older women have worse cosmetic results than younger women.¹ One problem in younger women is that as the patient ages the normal contralateral breast tends to increase in size, whereas the treated breast tends not to and some treated breasts shrink. A treated breast that is symmetrical immediately following treatment can thus become asymmetrical over time.

There is a trend towards increased fibrosis in larger breasts, which leads to poorer cosmetic results than seen in smaller breasts.⁶³ For this reason large-breasted women may be best treated by an operation that excises their cancer and at the same time reduces the volume of the breast (therapeutic mammaplasty). The best option to achieve symmetry in such women is to reduce both breasts through reduction-type incisions. Better cosmetic results following breast-conserving surgery and radiotherapy are obtained in medium- and moderate-sized breasts; achieving a good cosmetic outcome can often be a problem in small breasts.¹

Tumour factors

Increasing tumour size means that increasingly large amounts of tissue have to be removed. The volume of tissue excised is the most important factor relating to cosmetic outcome and so not surprisingly patients with larger tumours tend to have worse cosmetic results than women with smaller cancers.^64,65 There are some data indicating that in surgery for small and impalpable cancers, a disproportionately large amount of normal surrounding breast tissue is removed to ensure that all the affected tissue is excised. The role of the surgeon is to excise the cancer completely in as small a volume as possible. Removing large volumes of tissue when excising small screen-detected cancers is not satisfactory surgical practice.

Surgical factors

The poorer cosmetic results obtained with quadrantectomy, even in the most experienced hands, compared with wide excision are well documented and are related to the much larger volumes of tissue removed by quadrantectomy.⁶⁹

Even more critical than the volume of tissue resected is the percentage volume of the breast excised. There is a highly statistical correlation between cosmetic outcome and percentage volume of the breast excised (Fig. 4.8), with excisions of less than 10% of breast volume generally being associated with a good cosmetic outcome, whereas excisions over 10% often produce a poor cosmetic result (Fig. 4.9). Where it is clear that more than 10% of breast volume needs to be excised in order to remove the cancer, then consideration should be given to one of a number of procedures that can improve the final cosmetic result. These include volume replacement with a myocutaneous or local lipocutaneous flap,^12,13 volume replacement using immediate lipofilling following the tumour excision, an oncoplastic reduction procedure (therapeutic mammoplasty), neoadjuvant drug therapy or a mastectomy with or without immediate reconstruction.

Breast-conserving surgery after neoadjuvant therapy

Significant numbers of patients are diagnosed with large or locally advanced breast cancer, many of whom are treated initially by neoadjuvant chemotherapy or endocrine therapy. Up to a half of these patients will subsequently become candidates for breast-conserving surgery. To improve complete excision rates and minimise cosmetic deformity in these patients there are some guiding principles when performing breast conservation surgery after completion of neoadjuvant therapy. First, it is important to know the exact site of the tumour within the breast, as significant numbers of patients with HER2-positive and triple negative cancers will have a complete pathological response. All patients undergoing neoadjuvant chemotherapy who might be candidates for subsequent breast-conserving surgery should therefore have one or more tumour markers placed centrally prior to or early during treatment. The patterns of response to neoadjuvant chemotherapy and neoadjuvant endocrine therapy differ.⁷² The most common form of pathological change in patients undergoing neoadjuvant endocrine therapy is central scar formation,⁷² which results in concentric reduction in tumour size and tumour volume. Breast-conserving surgery following neoadjuvant endocrine therapy is therefore usually successful at excising all disease in one operation and few patients have involved margins. In contrast, a significant number of patients after neoadjuvant chemotherapy have a diffuse pattern of response to chemotherapy, with reduction in tumour cellularity but without significant shrinkage of volume. This diffuse tumour may be impalpable and more than 25% of patients undergoing breast-conserving surgery after neoadjuvant chemotherapy will have incomplete excision of disease. All patients undergoing breast-conserving surgery after neoadjuvant chemotherapy should be warned of this rate of incomplete excision and the possible need for a further operation.

Radiotherapy

Increasing doses of radiotherapy, particularly with the addition of boost, have a detrimental effect on cosmetic outcomes.^31,63,64 Long-term follow-up is necessary to assess cosmetic outcome; 3 years after treatment, radiotherapy effects tend to stabilise. Fibrosis is a late effect of radiotherapy and produces breast retraction and contour distortion. The treated breast tends not to increase in size to the same extent as the opposite untreated breast, so patients as they age can develop asymmetry even when the initial cosmetic result was excellent. Boost has a negative impact on cosmesis because it produces intense fibrosis and unsightly skin changes, including telangiectasia.³¹

Other treatment effects

Tamoxifen and aromatase inhibitors have little if any effect on cosmetic outcome, whereas some studies have suggested that chemotherapy has a negative impact on the cosmetic outcome of breast-conserving surgery.¹

Treatment of poor cosmetic results after breast-conserving surgery

Prevention is better than treatment, so minimising volume, closing breast defects and immediate lipofilling (Fig. 4.10) are much better options than trying to correct asymmetry once it has developed. Options for improving poor cosmetic outcomes include increasing the volume of one or both breasts if the main problem is essentially loss of volume rather than significant radiation fibrosis. While placement of silicone prosthesis or prostheses has been described, they are successful only for patients with little or no deformity and absence of marked skin changes.⁷⁴ Swelling following implant insertion in a radiotherapy-treated breast is often marked and takes many months to settle. Some patients develop marked capsular contraction after implant placement following radiotherapy but there are no data on whether this incidence is greater than in women having augmentation with no prior radiotherapy. The use of implants has been largely superseded by lipofilling. Fat is aspirated from the abdomen and thighs and centrifuged, washed or filtered.^75,76 Having removed the oil and blood it is then injected as microdroplets into the area of distortion and/or asymmetry. Approximately 40% of the injected fat survives. Multiple episodes of lipofilling combined with scar release or scar excision are often required to correct significant breast deformity and asymmetry (Fig. 4.11).⁷⁶ If the problem is simply one of asymmetry and the treated breast is a satisfactory shape but smaller than the normal contralateral breast, then the contralateral breast can be reduced. If the treated breast is shrunken, misshapen and scarred, then another option is to excise part or the whole of the treated breast and reconstruct either part of the breast or the whole breast. Pedicled myocutaneous latissimus dorsi or transverse rectus abdominis myocutaneous (TRAM) flaps offer an opportunity to excise unsightly areas of skin and/or breast distortion and scarring, and provide one option to regain symmetry (Fig. 4.12).

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