S10 Session 7. Surgery of breast cancer: Focus on controversies Friday, 18 March 2011

[10] Waljee JF, Hu ES, Ubel PA et al. Effect of esthetic outcome after breast-conserving surgery on psycho social fuctioning and quality of life. J ClinOncol 2008; 26: 3331−7.

S25 Immediate breast reconstruction after mastectomy

P. Veronesi1, F. De Lorenzi2, F. Magnoni2, G. Lissidini2, P. Caldarella2.1Department of Breast Surgery, 2European Institute of Oncology, Milan,Italy

Aims: We present a brief overview of the current state of postmastectomyimmediate reconstruction, which is actually an integral part of breastcancer treatment with positive aesthetic and psychosocial effects. Thepreservation of the inframammary fold and the conservation of the skinenvelope and nipple areola complex has led to improved cosmetic resultsfollowing both autologous and implant-based reconstruction.There is a general agreement for immediate breast reconstruction in

case of in situ tumors, while the reconstruction is often delayed in casesof invasive cancers or contraindicate in the elderly cohort.Second endpoint of this review is to investigate the safety of immediate

postmastectomy reconstruction for invasive cancers and in the elderlypopulation.

Methods and results: We reviewed our series and the recent literatureon this topic. While there is a general consensus that advanced age is nota contraindication to immediate reconstruction and breast reconstructioncan be successfully performed on well-selected elderly patients, mostoncologists in Europe do not prefer immediate reconstruction for invasivecarcinoma, advocating the risk of delay of the medical adjuvant treatment incase of complications due to the reconstructive procedure. Our experienceand a lot of studies suggest that immediate breast reconstruction is a safeand reliable treatment option in case of invasive cancers. However, if post-mastectomy irradiation is necessary on the basis of the final pathologicalfinding, this is associated with a high rate of surgical complications andimplant loss among patients who underwent immediate reconstruction withprostheses. Moreover, current evidence suggests that postmastectomyradiation therapy also adversely affects autologous tissue reconstruction.

Conclusions: Immediate breast reconstruction after mastectomy is anintegral part of the complete management of breast cancer. Determiningthe risk of postmastectomy irradiation prior to definitive resection andreconstructive operations may reduce complications and improve aestheticoutcomes by guiding surgical decision making.

Keywords: immediate reconstruction, mastectomy, invasive cancer, el-derly.Disclosure of Interest: None Declared

S26 Prophylactic mastectomy of the contralateral breast

M. Morrow1. 1Breast Service, Department of Surgery, MemorialSloan-Kettering Cancer Center, New York, United States

The use of contralateral prophylactic mastectomy (CPM) in the UnitedStates is increasing in women with DCIS and stage 1−3 breast cancer,in spite of the fact that the widespread use of adjuvant therapy hasmade contralateral breast cancer an infrequent event. In a population-based study of 134,501 women with unilateral DCIS and stage 1 and 2cancer, the 10-year actuarial risk of a second cancer was 6.1%. Even in“high-risk” subgroups such as women under age 45 years at diagnosis orthose with lobular cancer, 10-year risks were 6.2% and 6.4%, respectively.Endocrine therapy reduces contralateral cancer by 50−60%, conventionalchemotherapy by 20%, and trastuzumab appears to decrease risk by 50%,meaning that older studies done prior to the use of these agents in small,node-negative breast cancers overestimate risk. For most women, the riskof death from the index cancer and the risk of non-cancer death greatlyexceeds the risk of death from contralateral cancer, making CPM unlikelyto decrease breast cancer mortality.We examined all patients undergoing mastectomy for unilateral cancer

at Memorial Sloan-Kettering Cancer Center between January 1997 andDecember 2005 to compare the characteristics of those who did (n = 407)and did not (n = 2558) undergo CPM.During the study period the rate of CPM increased from 7% to 24%.

Patients undergoing CPM were younger (45.6 years versus 54.7 years),more likely to be Caucasian, and more likely to have a family historyof breast cancer, although only 8% had 2 or more affected first-degree

relatives. Only 52 (13%) could be characterized as truly high risk based ondocumented BRCA mutation or a history of mantle irradiation. Treatmentfactors including having an MRI at diagnosis, a failed attempt at breastconservation, or undergoing reconstruction were significantly associatedwith CPM. At median follow-up of 6 years only 12 (0.4%) of the patientsnot having CPM developed a contralateral cancer. In contrast, 7% of theno-CPM group and 4% of the CPM group developed metastatic disease.Our data do not support the idea that increased awareness of risk is

responsible for rising rates of CPM. Improved patient education regardingthe low risk of contralateral cancer, the effect of systemic treatment onlowering risk, and competing causes of mortality is indicated.Disclosure of Interest: None Declared

S27 Positive axillary sentinel lymph node: Is axillary dissectionalways necessary?

V. Galimberti1. 1European Institute of Oncology, Molecular Senology,Milano, Italy

There is considerable interest in foregoing axillary dissection (AD) whenthe sentinel node (SN) is positive in early breast cancer, particularlywhen axillary involvement is minimal (micrometastases or isolated tumorcells). In fact clinical practice has run ahead of the evidence, since recentSEER data indicate that axillary dissection is ‘underused’ in breast cancerpatients with micrometastases. Several trials are addressing the problem(IBCSG 23−01, ASCOG Z0011, EORTC AMAROS and EORTC POWER).Only Z0011 has published interim results, finding, after a median follow-up of 6.3 years, no differences in locoregional recurrence or regionalrecurrence between patients, with a positive SN, who received AD or nofurther axillary treatment. Our own retrospective study evaluated patientswith micrometastases or isolated tumor cells in the SN who received noaxillary treatment. We found high five-year survival and low cumulativeincidence of axillary recurrence, supporting the findings of Z0011 andproviding justification for the increasingly common practice of foregoingAD in women with minimal SN involvement. It is important to sound anote of caution however: We believe that axillary dissection is not alwaysnecessary in women with a positive axilla but it is important to reliablyidentify the subset of patients at high risk of developing overt axillarydisease. The IBCSG 23−01 and EORTC AMAROS (still in follow-up) maybe able to identify high risk patients who would should receive elective AD.Disclosure of Interest: None Declared

S28 Local therapy for breast cancer in malignant lymphomasurvivors

M. Intra1, V. Galimberti1, P. Veronesi1, R. Orecchia2, S. Zurrida1,U. Veronesi3. 1Department of Breast Surgery, European Institute ofOncology, 2Department of Radiotherapy, 3European Institute of Oncology,Milan, Italy

Patients who have undergone mantle radiotherapy for Hodgkin’s diseaseare at increased risk of developing breast cancer. In such patients, breastconserving surgery followed by breast irradiation is generally consideredcontraindicated owing to the high cumulative radiation dose. Mastectomyis therefore recommended as the first option treatment in these women.To evaluate safety and effectiveness of breast conserving surgery asso-

ciated with full-dose intraoperative radiotherapy in order to avoid unneces-sary mastectomies in patients previously irradiated for Hodgkin’s diseasewho develop breast cancer.Forty four patients affected by early breast cancer previously treated

with mantle radiation for Hodgkin’s disease underwent breast conservingsurgery associated with full-dose intraoperative radiotherapy with electrons(ELIOT). Post operative whole breast irradiation was omitted. A total doseof 21Gy in 39 cases, 18Gy in 3 cases and 17Gy in 2 cases weredelivered directly to the mammary gland without acute complications andwith good cosmetic results. After an average of 43.7 months of follow up,no local late sequelae were observed. In 3 cases an ipsilateral breasttumor reappearence was observed. In 2 more cases a contralateral breastcarcinoma developed and one patient died due to the progression of thedisease.In patients previously irradiated for Hodgkin’s disease, intraoperative

radiotherapy with electrons (ELIOT) can avoid repeat irradiation of the

Friday, 18 March 2011 Session 8. Local treatments: Further evolution S11

whole breast, permit breast conserving surgery and decrease the numberof avoidable mastectomies.Disclosure of Interest: None Declared

Friday, 18 March 2011 11.00–12.30

Session 8. Local treatments:Further evolution

S29 Intraoperative radiation therapy: Is it a standard now?

R. Orecchia1. 1Radiation Oncology, European Institute of Oncology &University, Milan, Italy

Over the past ten years a increasing number of papers have beenpublished detailing various approaches of Partial Breast Irradiation (PBI),utilizing accelerated fractionated external beam radiation therapy or sin-gle dose intraoperative (IORT) or brachytherapy techniques. Despite thelacking of mature Phase III clinical data, very recently both the Americanand European Societies for Therapeutic Radiology and Oncology (AS-TRO & ESTRO) have developed, independently, some recommendationsproviding a clinical guidance for the use of PBI outside the context ofa clinical trial [1,2]. With some minor differences, ASTRO and ESTROguidelines proposed the selection criteria to define a low-risk group ofpatients, suitable to be treated in clinical setting. Main characteristicsare age over 50 years for ESTRO (60 years for ASTRO), small ductalcarcinoma (up to 3 cm and up to 2 cm, respectively) and negative axilla,wide free margins, no additional pathological risk factors, such as extensiveintraductal component, lympho-vascular invasion, BRCA mutation, andothers and, of course, unifocal/unicentric disease. Among the differenttechniques used to perform PBI, IORT has increased rapidly in popularity,mainly in Europe. IORT allows to realize a high radiation dose to theindex quadrant, eliminating the treatment to the tissue remote from thetumour bed, and using only one single session, as sole treatment (oranticipated boost). This may represent the possibility of overcoming someconstraints such as the accessibility to the centres of radiotherapy, thesocio-economic impact on the working life and on the personal habits of thepatient. Another important advantage is the avoidance of the interactionswith the systemic therapy, that may determine delays in the initiation orin the carrying out of the conventional treatment. These potential benefitsmust be balanced with the potential risk of recurrence within the untreatedgland tissue in the same breast as well as the unknown long-term cosmeticresults. A report of a randomized Phase III clinical trial, named TARGIT,even with still limited follow-up period, confirmed the equivalence in alow-risk group of patients of a intraoperative single dose of 20Gy, givenwith low-energy X-rays, on the tumour bed only when compared withconventional postoperative approach [3]. In addition, the results of the non-randomized ELIOT study from Milan using 21Gy intraoperative electronbeam identified a group of patients, based of detailed univariated andmultivariated analyses, suitable for the treatment [4]. The comparisonbetween the current standard for early stage breast cancer with earlydata coming from PBI and IORT techniques poses a dilemma as to whenpreliminary results are sufficiently mature to be allow practitioners andpatients to consider a new treatment approach as safe. We know that mostdata from controlled and/or randomized of breast conservation therapyhave demonstrated the importance of long-term data (up to 20 years) indetermining the ultimate efficacy of a treatment. Pressure to consider thepotential for PBI has come from within the radiation oncology community,as well as from surgeons, medical oncologists, and patients. Since upto now there were few study identifying groups of patients that wouldbenefit from this new approach, the general recommendation is not toconsider this technique as the therapeutic standard for all, but to limitthe use to proper selected patients. For this reason, further mature datacoming from the multi- or unicenter large phase III ongoing trials in USand Europe comparing standard irradiation with the different PBI/IORTschedules and techniques will hopefully support the movement into routineclinical practice. New issues of biology-oriented patient selection, imagingassessment for unifocal disease and target volume definition, and qualityassurance program should be also addressed and defined in designingnew generation of randomized trials.

References

[1] Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradia-tion consensus statement from the American Society for Radiation Oncology(ASTRO). Int J Radiation Oncol Biol Phys 2009, 74: 987–1001.

[2] Polgar C, Van Limbergen E, Potter R, et al. Patient selection for acceleratedpartial-breast irradiation (APBI) after breast-conserving surgery: recommen-dations of the Groupe Europeen de Curietherapie-European Society forTherapeutic Radiology and Oncology (GEC-ESTRO) breast working groupbased on clinical evidence (2009). Radiother Oncol 2010, 94: 264−73.

[3] Vaidya JS, Joseph DJ, Tobias JS, et al. Targeted intraoperative radiotherapyversus whole breast radiotherapy for breast cancer (TARGIT-A trial): aninternational, prospective, randomised, non-inferiority phase 3 trial. Lancet2010, 376 (9735): 91–102.

[4] Veronesi U, Orecchia R, Luini A, et al. Intraoperative radiotherapy duringbreast conserving surgery: a study on 1,822 cases treated with electrons.Breast cancer Res Treat 2010, 124: 141−51.

Disclosure of Interest: None Declared

S30 Abbreviated course of radiotherapy (RT) for breast cancer

J. Harris1, J. Schoenfeld2. 1Dana-Farber Cancer Institute and Brighamand Women’s Hospital, Harvard Medical School, Boston, MA, UnitedStates, 2Harvard Radiation Oncology Program, Harvard Medical School,Boston, MA, United States

The use of RT as a component of breast-conserving therapy or after mas-tectomy has been proven to reduce the risk of local-regional recurrence(LRR) and to improve long-term breast cancer-specific and overall survival.As has been the common practice in the United States and ContinentalEurope, the majority of studies that demonstrated these benefits utilizeddaily radiation doses ranging from 1.8−2Gray (Gy). However, due togeographic limitations, patient preferences and financial considerations,there have been continued attempts to evaluate the efficacy and toxicity ofabbreviated courses of breast RT. Two key factors in these attempts havebeen: (1) advances in radiobiology allowing for a more precise estimationof equivalent dosing; and (2) advances in the delivery of RT that haveresulted in substantially improved dose homogeneity in the target volume.As an alternative to approximately five weeks of daily treatment at

1.8−2Gy, delivering radiobiologically-equivalent total doses in hypofrac-tionated, abbreviated schedules has been evaluated in five randomizedcontrolled trials (Table 1), as well as many prospective and retrospec-tive experiences. These studies have generally demonstrated equivalentrates of LRR, disease-free survival and overall survival with the use ofhypofractionated regimens. Despite theoretical and historic concerns thathypofractionated regimens could increase damage to normal tissue, therates of acute and long-term toxicities have generally not been increasedin most recent series. Some toxicities, however, may take years to decadesto manifest.

Table 1. Randomized trials evaluating hypofractionated breast radiotherapy

Trial (no. ofpatients)

Median follow-up(IQ range)

Fractionationschedules

Ipsilateral breasttumor control

Disease-freesurvival

Overallsurvival

Canadian(1234)

12 yrs(NS)

25×Gy16×2.67Gy

93.3% @ 10 yrs93.8%

NS 84.4%84.6%

START A(2236)

5.1 yrs(4.4−6 yrs)

25×2Gy13×3Gy13×3.2Gy

96.4% @ 5 yrs94.8%96.5%

86.4%84.8%88%

88.9%89.3%88.7%

START B(2215)

6.0 yrs(5−6.2 yrs)

25×2Gy15×2.67Gy

96.7% @ 5 yrs97.8%

85.9%89.4%

89%92%

RMH/GOC(1410)

9.7 yrs(7.8−11.8 yrs)

25×2Gy13×3Gy13×3.3Gy

87.9% @ 10 yrs85.2%90.4%

NS NS

Hopital Necker(230)

Minimum 4yrs 25×1.8Gy*4×5.75Gy*

95%93%

NS NS

*Interstitial brachytherapy (20Gy) given to patients who did not receive mastectomy.Abbreviations: IQ – intraquartile; yrs – years; NS – not specified; Gy – Gray; START –Standardization of Breast Radiotherapy; RMH/GOC – Royal Marsden Hospital/GloucesterOncology Center; ER – estrogen receptor.

Questions still remain regarding which patients are appropriate forabbreviated treatment. The majority of patients included in the studiessupporting hypofractionated treatment were of older age with early-stageinvasive ER+ disease of predominantly lower histologic grade. This fa-vorable subset of patients is also the most eligible for other alternativetreatment approaches, such as partial-breast irradiation or hormonal ther-apy alone. Additionally, few to none of the patients included in most studies