International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission : results of a multivariate analysis.

BACKGROUND: An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. PATIENTS AND METHODS: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. RESULTS: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). CONCLUSION: pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.

[Case reports of operative management of very large, benign phylloid tumors--is a safety margin necessary?]. / Fallberichte über operatives Management bei sehr grossen, benignen Phylloidtumoren--Ist ein Sicherheitssaum notwendig?

The phylloid tumor (PT, formerly called cystosarcoma phylloides) is a rare neoplasia of the female breast. Usually the PT is treated with breast-conserving surgery. In spite of progress in early diagnosis, PTs recur frequently--independently of tumor's degree of malignancy. Especially in cases of malignant PT, complete resection with tumor-free margins is seen as the only predictive marker for tumor recurrence or metastases. Benign PT is also often resected with wide tumor-free margins. Because of the tumor's occasionally enormous dimensions, this therapy concept makes breast-conserving surgery almost impossible. A simple enucleation of benign PT is an option to facilitate the preservation of breast tissue and a cosmetically satisfactory breast reconstruction. In the case of particularly large benign PT, enucleation even without wide margins prevents tumor recurrence.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Remission rates following preoperative chemotherapy and radiation therapy in patients with breast cancer.

PURPOSE: To evaluate remission and breast-conservation rates after preoperative chemotherapy or chemo-radiotherapy (CT-RT). PATIENTS AND METHODS: Seventy-three patients with 74 biopsy-proven invasive breast cancers prospectively entered the protocol. Eighteen patients were treated by neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (chemotherapy group). Fifty-five patients with 56 tumors were treated with combined neoadjuvant chemo-radiotherapy, followed by surgery (chemo-radiotherapy group). Most patients of both treatment groups received 4 cycles of EC chemotherapy. In some patients with large tumors 3 cycles of CMF were added. Chemotherapy was followed by hormonal treatment with tamoxifen or LHRH agonists in case of positive hormone-receptor status. Preoperative radiotherapy was administered using 2 Gy fractions up to a total dose of 50 Gy, followed by a tumor boost of 6 to 11 Gy. The median overall treatment time was 41 days (range: 35 to 55 days). The median time interval between end of neoadjuvant therapy and surgery was 11 weeks (range: 10 to 22 weeks) and 27 weeks (range: 11 to 41 weeks) for the chemotherapy- and chemo-radiotherapy group. The median time interval between end of chemotherapy and the beginning of irradiation ranged between 2 and 8 weeks (median 4 weeks) in the chemo-radiotherapy group. RESULTS: Side-effects due to chemo- or radiotherapy were moderate and reversible. In the chemotherapy group 17/18 patients (94%) achieved a partial (pPR) and 1/18 patients (6%) a complete histopathological response (pCR). In the chemo-radiotherapy group 32/56 (57%) showed a pPR and 24/56 (43%) a pCR. The difference in complete remission is significant (Fisher's Exact Test: p = 0.004). In 45/74 cases (61%) the breast was preserved, immediate breast reconstructions with rectus myocutaneous flaps (TRAM) after mastectomy were performed in 8/74 cases (11%) and modified radical mastectomies without reconstruction were required in 21/74 cases (28%). The breast conservation rates were similar in both treatment groups. CONCLUSIONS: Even though the small number of patients in the present protocol does not permit definite conclusions, the results of combined modality treatment seem promising with regard to tumor remission within the treated breast and as a tool for breast conservation in advanced stage disease. On the basis of these encouraging data a prospective Phase-III study has been initiated.

Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven useful in the differentiation of various tumour entities, including breast cancer. In patients with primary breast cancer we performed a 3-h imaging protocol to examine possible improvements in tumour detectability and image contrast. Twenty-nine patients with primary breast cancer with a diameter of >/=2 cm that was demonstrated to be malignant by biopsy or surgery were injected with 370-740 MBq 18F-FDG and scanned in the prone position. Data were acquired 0-40 min, 1.5 h and 3.0 h after injection. After correction for measured attenuation, decay and scatter and iterative reconstruction, standardised uptake values (SUVs) and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual analysis was performed using transverse, sagittal and coronal slices as well as 3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were significantly higher for the 3-h images than for the 1.5-h images. SUVs did not increase to the same extent. Lesion detectability was 83% in 1.5-h images compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i.

An approach to the repair of partial mastectomy defects.

In many cases, breast deformity caused by partial mastectomy can be reduced or corrected by plastic surgery. Partial breast reconstruction is best performed immediately after the partial mastectomy using an approach determined by the size of the breast and the defect. Small defects in large breasts usually need no reconstruction. For larger defects in large breasts, breast reshaping (similar to reduction mammaplasty) combined with a contralateral breast reduction is usually the best option. For medium-sized or smaller breasts with small to moderate-sized defects, local flaps from the subaxillary region are very useful. If the defect is too large for correction with local tissue, a latissimus dorsi myocutaneous flap is usually the best choice. Using these techniques, patients can achieve aesthetically better outcomes from breast-conservation therapy, even when larger tumors are being treated or when wider margins are taken to reduce the risk of tumor recurrence. By working together with an oncologic surgeon and facilitating the removal of larger tumors, the plastic surgeon can widen the indications for both breast-conservation therapy and breast reconstruction at the same time.

Induction chemotherapy and radiotherapy to avoid mastectomy in stage IIA-IIIA breast cancer.

The aim of the presented protocol was to investigate tumour remission and breast conservation rates with and without flap supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. 101 patients with stage IIA-IIIA breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. 96 patients underwent salvage surgery. Complete pathologic response was not related to tumour diameter at diagnosis, the applied chemotherapy regime, number of chemotherapy cycles, overall radiation treatment time and time interval between radiotherapy and surgery. A breast conserving approach was possible in 55 patients (54%). After a median follow-up of 18 months no patient developed an isolated local recurrence.

[Preoperative irradiation and interstitial radiotherapy-hyperthermia boost in breast tumors > or = 3 cm. The Düsseldorf experience]. / Präoperative Bestrahlung mit interstitiellem Radio-hyperthermie-Boost bei Mammatumoren > or = 3 cm. Düsseldorfer Ergebnisse.

AIM: The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. PATIENTS AND METHODS: One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy 192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 x 2 Gy/week. Local hyperthermia with 43.5-44.5 degrees C over 60 minutes was delivered immediately before interstitial radiotherapy. RESULTS: One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases. CONCLUSION: In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.

[MR mammography of fatty tissue necrosis]. / MR-Mammographie der Fettgewebsnekrose.

PURPOSE: To evaluate MR-imaging for the differentiation of fatty necrosis (FN) of the breast. MATERIAL AND METHODS: In 1016 MR mammographies FN was found in 13 patients aged 44 to 69 years. In all studies we used a proton-weighted fat suppressed sequence (STIR) and serial T1-weighted gradient echo sequences before and after bolus injection of Gd-DTPA, MRI was correlated to ultrasound and in 8 cases to mammographic findings. RESULTS: All 15 FN displayed fat-isointense signal on T1-weighted and on proton-weighted, fat-suppressed sequences. They were delineated by a more or less wide rim of low signal intensity with sharp border to the center. After intravenous injection of gadopentetate dimeglumine they showed no increase of signal intensity in the centre and no increase, or only a minor increase, of the rim. Ultrasound could not distinguish FN from recurrent tumour in 6 cases. 7 FN looked like atypical cysts. CONCLUSION: MR-mammography is very promising in the diagnosis of FN.

[MR-mammography assessment of tumor response after neoadjuvant radiochemotherapy of locally advanced breast carcinoma]. / MR-mammographische Beurteilung des Tumoransprechverhaltens nach neoadjuvanter Radiochemotherapie lokal fortgeschrittener Mammakarzinome.

PURPOSE: We investigated the role of magnetic resonance mammography in monitoring tumour response of locally advanced breast cancer (LABC) after neoadjuvant radiochemotherapy. MATERIAL AND METHODS: 17 patients with LABS had a magnetic resonance mammography and ultrasonography before and after neoadjuvant radiochemotherapy. RESULTS: After neoadjuvant radiochemotherapy 14 patients showed in MR-mammography less pronounced and prolonged enhancement without washout. After treatment three patients had signal intensity-time curves still characteristic for tumour. Ultrasonography was true negative in two patients, true positive in 12 and false positive in three patients. CONCLUSION: Magnetic resonance mammography is suitable for monitoring tumour response after radiochemotherapy of LABC. However, a negative MRI does not exclude a residual tumour. Ultrasonography is of limited value in monitoring therapy of LABC.

[Initial experiences with MR-mammography in after-care following surgical flap treatment of breast carcinoma]. / Erste Erfahrungen mit der MR-Mammographie in der Nachsorge bei lappenunterstützter operativer Behandlung des Mammakarzinoms.

PURPOSE: To demonstrate typical MR mammographic findings after plastic surgery of breast cancer. PATIENTS AND METHODS: Postoperative (7-38 months, median 13) MR mammographic examinations of 25 patients operated for breast cancer (11 latissimus dorsi-flaps (LAT), 14 rectus abdominis myocutaneous-flaps (TRAM)), were reevaluated. The examinations were performed with a breast coil at 1 T. The sequences applied were a fat-suppressed 2-D turbo IR-sequence proton-weighted and a T1-weighted FLASH 3-D sequence as dynamic series. RESULTS: Scars between the myocutaneous flap and the remaining breast tissue always appeared in form of a ligament or septum. Signal and perfusion characteristics of scar tissue and muscle stalk in this investigation were clearly different from those of tumour. One tumour recurrence and one fat necrosis was found and rectified by biopsy. CONCLUSION: MR mammography is a very valuable diagnostic method for postoperative evaluation of myocutaneous flap-based therapy of breast cancer.

[Radiotherapy following a breast-preserving operation in breast carcinoma]. / Strahlentherapie nach brusterhaltender Operation beim Mammakarzinom.

Between 1980 and 1988, 116 patients with invasive breast cancer were treated by limited surgery with axillary node dissection followed by radiation therapy. Radiotherapy was performed by individually computerized treatment planning. The target volume dose was 50 Gy to the whole breast followed by an electron boost of 10 Gy to the tumor bed. The median follow-up period was 59 months. The actuarial overall survival rate is 93%, and the disease-free survival 75.2%. Ten (8.6%) breast recurrences occurred. Analysis of clinical and pathological prognostic factors revealed that local control was impaired by young age, negative hormone receptors, G3-4 tumors and intraductal growth. The recurrence rate for T3- and T4-tumors was 12.5%.

[The ultrasonic diagnosis of breast prosthesis implanted after operative treatment of tumors or augmentation plastic of the breast (author's transl)]. / Ultraschalldiagnostik bei Mammaprothesen nach operativer Behandlung von Mammatumoren oder Augmentationsplastik

The ultrasonic diagnosis as a method of recognising postoperative subprosthetical breast pathological changes (respectively of simulated tumor recidivs and implanted breast prosthesis) located near the thorax and therefore difficult to detect by external palpation and mammography examination have been described in a follow-up study, and further possibilities of application suggested.